80 research outputs found

    Do neuropsychological tests detect preclinical Alzheimer's disease: Individual-test versus cognitive-discrepancy score analyses.

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    Attempts to identify cognitive markers of a preclinical phase of Alzheimer’s disease (AD) have yielded inconsistent findings. The problem may stem in part from methodologies that are insensitive to potential subgroups within the at-risk, preclinical AD population (PCAD). The present study investigated the utility of asymmetric cognitive profiles in identifying individ-uals at risk for AD. Twenty elderly adults who were later diagnosed with AD (PCAD) and 20 matched control participants were compared on measures of cognitive asymmetry derived from difference scores on tests of verbal and visuospatial ability. Although both groups performed similarly on the individual tests, comparisons using difference scores revealed significantly larger discrepancies between naming and visuoconstruction skills in the PCAD group. The PCAD group also had a higher frequency of asymmetric cognitive profiles relative to a normative group. Subtle cognitive changes can precede the onset of Alz-heimer’s disease (AD) by as many as 7 to 10 years (Elias et al., 2000; Linn, Wolf, Bachman, & Knoefel, 1995). Find-ings of a long prodromal period have fostered new researc

    Gene-Based Analysis of Regionally Enriched Cortical Genes in GWAS Data Sets of Cognitive Traits and Psychiatric Disorders

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    Background: Despite its estimated high heritability, the genetic architecture leading to differences in cognitive performance remains poorly understood. Different cortical regions play important roles in normal cognitive functioning and impairment. Recently, we reported on sets of regionally enriched genes in three different cortical areas (frontomedial, temporal and occipital cortices) of the adult rat brain. It has been suggested that genes preferentially, or specifically, expressed in one region or organ reflect functional specialisation. Employing a gene-based approach to the analysis, we used the regionally enriched cortical genes to mine a genome-wide association study (GWAS) of the Norwegian Cognitive NeuroGenetics (NCNG) sample of healthy adults for association to nine psychometric tests measures. In addition, we explored GWAS data sets for the serious psychiatric disorders schizophrenia (SCZ) (n = 3 samples) and bipolar affective disorder (BP) (n = 3 samples), to which cognitive impairment is linked. Principal Findings: At the single gene level, the temporal cortex enriched gene RAR-related orphan receptor B (RORB) showed the strongest overall association, namely to a test of verbal intelligence (Vocabulary, P = 7.7E-04). We also applied gene set enrichment analysis (GSEA) to test the candidate genes, as gene sets, for enrichment of association signal in the NCNG GWAS and in GWASs of BP and of SCZ. We found that genes differentially expressed in the temporal cortex showed a significant enrichment of association signal in a test measure of non-verbal intelligence (Reasoning) in the NCNG sample. Conclusion: Our gene-based approach suggests that RORB could be involved in verbal intelligence differences, while the genes enriched in the temporal cortex might be important to intellectual functions as measured by a test of reasoning in the healthy population. These findings warrant further replication in independent samples on cognitive traits
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