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

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

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

Response bias and aging on a recognition memory task

Response bias reflects the decision rule an individual uses when faced With uncertainty oil recognition memory tasks. Recent studies indicate frontal regions may mediate response bias performance. One theory of aging also implicates frontal lobe contributions in age-related cognitive changes. This suggests that frontal lobe changes may mediate response bias in older adults. Consistent with this frontal aging hypothesis. we predicted that response bias would become more liberal with age. Methods: Participants were 181 younger(30-49) and 112 older normal adults (75+) that were part of the California Verbal Learning Test-second edition (CVLT-2) normative sample (total n = 1078). We used parametric measures of discriminability and response bias provided by the CVLT-2 scoring program. Groups were similar in IQ and education. Multi-level regression models were created to examine the effects of moderating variables. The interaction between age and age group significantly predicted response bias. Post hoc analysis indicated that increasing age was associated with more liberal bias in the older but not in the younger group. In the light of reported relationships between frontal regions and both aging and response bias. we hypothesize that frontal changes may be the underlying mechanism explaining the increase in liberal response bias with age

Mechanisms of Memory Dysfunction during High Altitude Hypoxia Training in Military Aircrew

ObjectivesCognitive dysfunction from high altitude exposure is a major cause of civilian and military air disasters. Pilot training improves recognition of the early symptoms of altitude exposure so that countermeasures may be taken before loss of consciousness. Little is known regarding the nature of cognitive impairments manifesting within this critical window when life-saving measures may still be taken. Prior studies evaluating cognition during high altitude simulation have predominantly focused on measures of reaction time and other basic attention or motor processes. Memory encoding, retention, and retrieval represent critical cognitive functions that may be vulnerable to acute hypoxic/ischemic events and could play a major role in survival of air emergencies, yet these processes have not been studied in the context of high altitude simulation training.MethodsIn a series of experiments, military aircrew underwent neuropsychological testing before, during, and after brief (15 min) exposure to high altitude simulation (20,000 ft) in a pressure-controlled chamber.ResultsAcute exposure to high altitude simulation caused rapid impairment in learning and memory with relative preservation of basic visual and auditory attention. Memory dysfunction was predominantly characterized by deficiencies in memory encoding, as memory for information learned during high altitude exposure did not improve after washout at sea level. Retrieval and retention of memories learned shortly before altitude exposure were also impaired, suggesting further impairment in memory retention.ConclusionsDeficits in memory encoding and retention are rapidly induced upon exposure to high altitude, an effect that could impact life-saving situational awareness and response. (JINS, 2017, 23, 1-10)

Differentiation of Alzheimer's, Huntington's, and Parkinson's Disease Patients on the Basis of Verbal Learning Characteristics

This study examined the degree to which patients with dementia could be differentiated on the basis of their verbal learning characteristics. Patients with Parkinson's disease (PD), Huntington's disease (HD), and probable Alzheimer's disease (AD) were administered the California Verbal Learning Test. PD and HD patients were divided into subgroups to control for the severity of overall memory impairment. Discriminant function analysis correctly categorized over 76% of cases. Intrusions, perseverations, and rate of forgetting were the most discriminating variables. Profile differences between HD and PD were sufficiently robust to separate these two groups with reasonable accuracy. These results do not support a simplistic cortical-subcortical dichotomy; rather, individual dementing syndromes have unique patterns of verbal learning performance that are distinct from one another

Response bias and aging on a recognition memory task

Response bias reflects the decision rule an individual uses when faced With uncertainty oil recognition memory tasks. Recent studies indicate frontal regions may mediate response bias performance. One theory of aging also implicates frontal lobe contributions in age-related cognitive changes. This suggests that frontal lobe changes may mediate response bias in older adults. Consistent with this frontal aging hypothesis. we predicted that response bias would become more liberal with age. Methods: Participants were 181 younger(30-49) and 112 older normal adults (75+) that were part of the California Verbal Learning Test-second edition (CVLT-2) normative sample (total n = 1078). We used parametric measures of discriminability and response bias provided by the CVLT-2 scoring program. Groups were similar in IQ and education. Multi-level regression models were created to examine the effects of moderating variables. The interaction between age and age group significantly predicted response bias. Post hoc analysis indicated that increasing age was associated with more liberal bias in the older but not in the younger group. In the light of reported relationships between frontal regions and both aging and response bias. we hypothesize that frontal changes may be the underlying mechanism explaining the increase in liberal response bias with age