Cognitive Ability In Adulthood Research Articles

Replication study of candidate genes for cognitive abilities: the Lothian Birth Cohort 1936

As the proportion of older people in societies has increased, research into the determinants of cognitive ageing has risen in importance. Genetic influences account for over 50% of the variance in adult cognitive abilities. Previous studies on cognition and illnesses with cognitive impairments have identified single nucleotide polymorphisms (SNPs) within candidate genes that might influence cognition or age-related cognitive change. This study investigated 10 candidate genes in over 1000 Scots: the Lothian Birth Cohort 1936 (LBC1936). These participants were tested on general cognitive ability (Scottish Mental Survey 1947) at age 11. At mean age 70, they completed the same general cognitive ability test and a battery of diverse cognitive tests. Nineteen SNPs in 10 genes previously associated with cognition, Alzheimer's disease or autism were genotyped in 1063 individuals. The genes include BDNF, COMT, DISC1, KL, NCSTN, PPP1R1B, PRNP, SHANK3, SORL1 and WRN. Linear regression analysis investigated the additive effect of each SNP on the cognitive variables, covarying for gender and age. Childhood cognitive ability was also included as a covariate to identify associations specifically with cognitive ageing. Certain SNPs reached the conventional significance threshold for association with cognitive traits or cognitive ageing in LBC1936 (P < 0.05). No SNPs reached the Bonferroni-level of significance (all P > 0.0015). Of the 10 genes, we discuss that COMT, KL, PRNP, PPP1R1B, SORL1 and WRN especially merit further attention for association with cognitive ability and/or age-related cognitive change. All results are also presented so that they are valuable for future meta-analyses of candidate genes for cognition.

Oxidative stress and cognitive ability in adults with Down syndrome

Aims We aimed to study the hypothesis that high levels of superoxide dismutase (SOD1), previously reported in Down syndrome, would be associated with poorer ability on cognitive tests. Compensatory rises in the activity of glutathione peroxidase (GPx) was expected to be associated with better ability, so that a high ratio between SOD1 and GPx was hypothesised to be the best predictor of poorer cognitive performance. Methods 32 adults with Down syndrome between the ages of 18 and 45 years donated blood samples for SOD1 and GPx assays and urine for Isoprostane 8,12- iso-iPF 2α-VI assay, a specific biomarker of lipid peroxidation in vivo. Informants rated functional ability and memory function for all participants, and those adults with DS that was able to, also completed psychometric assessments of language ability and memory. Results Neither SOD1 nor GPx were related to the elevated markers of lipid peroxidation previously described in living adults with DS, and our hypothesis that an increased SOD1/GPx ratio would be correlated with worse performance on cognitive or functional measures was not supported. Contrary to our hypothesis, we found that low SOD1/GPx ratios were associated with worse memory ability, which remained after controlling for confounders such as sex, age or nutritional supplements. Conclusions The anti-oxidant system in DS is implicated in the cognitive phenotype associated with the chromosomal disorder, but the variations in the phenotype could result from several possible gene or gene product interactions. Much further research is required before it will be possible to counteract the oxidative stress associated with DS.

Apolipoprotein E is not Related to Memory Abilities at 70 Years of Age

APOE e4-related memory deficits were reported in a normal population aged between 50 and 60 when controlling for general cognitive ability in early adulthood. This extended findings of APOE e4 effects on cognitive ability in 60-80-year-olds to a younger group and confirmed that this effect relates to changes in memory ability with age. The present study tests the association of APOE e4 variation with verbal and spatial memory in a sample of 70-year-olds both adjusted and non-adjusted for childhood and adult general cognitive ability. The 1,013 participants comprise surviving members of the 1947 Scottish Mental Survey resident in the Lothian area of Scotland. They were tested on general cognitive ability at age 11 years and followed up at about age 70 with tests of verbal (immediate and delayed) and spatial memory. General linear models were used to test the association between variation in the APOE polymorphism (e4 presence vs. absence) and memory measures. Of the eight measures tested, Spatial span forward was significantly associated with APOE e4 variation (P = 0.04) when adjusting for IQ, whereas Logical memory immediate was associated with APOE e4 variation (P = 0.04) in the analysis not controlling for IQ. Neither of these tests was significant when a correction for multiple testing was applied. APOE e4 does not influence memory abilities in a normal population of 70-year-olds.

Minimal aberrant behavioral phenotypes of neuroligin‐3 R451C knockin mice

Neuroligin-3 is a member of the class of cell adhesion proteins that mediate synapse development and have been implicated in autism. Mice with the human R451C mutation (NL3), identical to the point mutation found in two brothers with autism spectrum disorders, were generated and phenotyped in multiple behavioral assays with face validity to the diagnostic symptoms of autism. No differences between NL3 and their wildtype (WT) littermate controls were detected on measures of juvenile reciprocal social interaction, adult social approach, cognitive abilities, and resistance to change in a spatial habit, findings which were replicated in several cohorts of males and females. Physical and procedural abilities were similar across genotypes on measures of general health, sensory abilities, sensorimotor gating, motor functions, and anxiety-related traits. Minor developmental differences were detected between NL3 and WT, including slightly different rates of somatic growth, slower righting reflexes at postnatal days 2-6, faster homing reflexes in females, and less vocalizations on postnatal day 8 in males. Significant differences in NL3 adults included somewhat longer latencies to fall from the rotarod, less vertical activity in the open field, and less acoustic startle to high decibel tones. The humanized R451C mutation in mice did not result in apparent autism-like phenotypes, but produced detectable functional consequences that may be interpreted in terms of physical development and/or reduced sensitivity to stimuli.

Predictors of Cognitive Ability in Adults Aging with HIV

Adults infected with HIV are living longer due to pharmacological advances, resulting in an increased potential for aging. Little is known about the effects of HIV infection and aging on cognition. Therefore, this pilot study assessed cognitive differences, symptoms of depression, and other measures of HIV-negative (n= 50) and HIV-positive adults (n= 50) who were 30 years of age or older. The normal convention of 50 years and over is used in HIV research to denote older adults and was used in this study as well. Self-rated questions as well as paper and pencil questionnaires were used to assess the study variables. Disease status of HIV-positive individuals was assessed through self-reported biological indicators. Depressive symptomatology had a significant association with cognitive decline; addressing these areas in adults aging with HIV may ameliorate cognitive ability. Surprisingly, age and CD4+ lymphocyte count were not predictive of cognitive performance. Controlling for education, gender, and depressive symptomatology, the HIV-positive group performed worse than the HIV-negative group on a number of cognitive tests. At present, cognitive interventions are being used to mitigate mental declines in older adults; similar techniques may be advantageous for those aging with HIV.

Current Awareness in NMR in Biomedicine

Current Awareness in NMR in Biomedicine

Rate of acquisition, adult age, and basic cognitive abilities predict forgetting: New views on a classic problem.

Rate of forgetting is putatively invariant across individuals, sharing few associations with individual-differences variables known to influence encoding and retrieval. This classic topic in learning and memory was revisited using a novel statistical application, multilevel modeling, to examine whether (a) slopes of forgetting varied across individuals and (b) observed individual differences in forgetting shared systematic relations with adult age, learning speed, and cognitive ability. Participants (N = 136) received mnemonic training prior to memorizing 4-digit numbers to perfection, and retention was tested immediately after training and after 30 min, 24 hr, 7 weeks, and 8 months. Slower rate of learning to criterion, older age, and poorer cognitive performance predicted accelerated forgetting with associations most pronounced within 24 hr from baseline. Observed correlates of differential forgetting slopes are similar to those previously found to affect encoding, suggesting continuity rather than asymmetry of prediction for these memory processes.

Hippocampal Myo-inositol and Cognitive Ability in Adults With Down Syndrome

Down syndrome (DS) is the most common genetic cause of mental retardation. However, the biological determinants of this are poorly understood. The serum sodium/myo-inositol cotransporter gene is located on chromosome 21, and myo-inositol affects neuronal survival and function. Nevertheless, few in vivo studies have examined the role of myo-inositol in DS. To determine if people with DS have significant differences in brain myo-inositol concentration from controls and if, within people with DS, this is related to cognitive ability. A case-control study. Outpatient. The sample was composed of 38 adults with DS without dementia (age range, 18-66 years) and 42 healthy controls (age range, 19-66 years). The DS and control groups did not differ significantly in age, sex, ethnic origin, apolipoprotein E status, or handedness. Hippocampal myo-inositol concentration and cognitive performance, as measured by the Cambridge Cognitive Examination. Hippocampal myo-inositol concentration was significantly higher in people with DS than in controls (P = .006), and within people with DS, increased myo-inositol concentration was significantly negatively correlated with overall cognitive ability (P = .04). Adults with DS have a significantly increased brain concentration of myo-inositol, and this is associated with reduced cognitive ability. Future studies are required to relate myo-inositol concentration in people with DS to brain development and increased risk for developing Alzheimer disease.

Does Methylphenidate Improve Inhibition and Other Cognitive Abilities in Adults with Childhood-Onset ADHD?

We examined the effect of methylphenidate (Mph) on inhibition and several other cognitive abilities in 43 adults with Attention Deficit Hyperactivity Disorder (ADHD) by use of Conners’ Continuous Performance Test (CPT) and the Change Task (ChT), an extension of the Stop Signal Test (SST). In a double blind, cross-over, placebo controlled study with Mph, tests were administered during the third week of individually titrated treatment with Mph (maximum dose 1 mg / kg / day) and during the third week of treatment with placebo. We established large medication effects for commission errors, standard error of mean reaction time, and attentiveness on the CPT, as well as moderate medication effects for mean reaction time on the CPT and response re-engagement speed on the ChT. For Stop Signal Reaction Time (SSRT) on the ChT, we also established large effects of Mph, but only in a group of participants who showed slow SSRTs on placebo. Mph indeed ameliorates inhibition, which is the core problem of ADHD, and certain other cognitive abilities in adults with ADHD. This research was supported by grants from Mental Health Institute GGZ Delfland, Health Insurance Company DSW, Nationaal Fonds Geestelijke Volksgezondheid (National Foundation for Mental Health), and De Hersenstichting (Brain Foundation). We thank Alex de Jager, Judith Rietjens, and Susan ter Linden for their help in collecting the data. We thank the Board of Scientific Activities of the Reinier de Graaf Hospital in Delft for their financial contribution to the preparation of the study medication. We thank Paul van der Linden for his help with the randomization procedure.

Quantitative Genetic Analysis of Latent Growth Curve Models of Cognitive Abilities in Adulthood.

Though many cognitive abilities exhibit marked decline over the adult years, individual differences in rates of change have been observed. In the current study, biometrical latent growth models were used to examine sources of variability for ability level (intercept) and change (linear and quadratic effects) for verbal, fluid, memory, and perceptual speed abilities in the Swedish Adoption/Twin Study of Aging. Genetic influences were more important for ability level at age 65 and quadratic change than for linear slope at age 65. Expected variance components indicated decreasing genetic and increasing nonshared environmental variation over age. Exceptions included one verbal and two memory measures that showed increasing genetic and nonshared environmental variance. The present findings provide support for theories of the increasing influence of the environment with age on cognitive abilities.

Absence of effect of depression on cognitive performance in early-stage Alzheimer disease.

Depression can interfere with the normal expression of cognitive abilities in adults of all ages, but it is unclear if depression in demented people, which is common, is associated with reduced cognitive performance beyond the effect of the dementia itself. To determine if depression adds to the cognitive deficit in dementia. Performance on psychometric tests of memory and other cognitive function was correlated with the number of depressive features reported by the individual and by a knowledgeable collateral source, as well as the judgment of a research clinician as to whether the person was depressed. An Alzheimer disease research center. The convenience sample included individuals with very mild (Clinical Dementia Rating, 0.5; n = 167 [mean age, 76.03 years]) or mild (Clinical Dementia Rating, 1; n = 155 [mean age, 78.41 years]) Alzheimer disease who were enrolled in ongoing longitudinal studies at the center. Psychometric measures of memory and cognition. Depression was present in 15% of the very mild and 24% of the mild dementia groups. There was no relation between the clinicians' diagnoses of depression and psychometric scores. Little relation was found between performance on the cognitive tests and the number of depressive features (maximum, 9) reported by the individual or collateral source. The few statistically significant (P<.05) correlations were modest (< or =0.21). Depression does not worsen cognitive test performance beyond the effect of dementia.

Effect of low doses of ionising radiation in infancy on cognitive function in adulthood: Swedish population based cohort study

Objective To determine whether exposure to low doses of ionising radiation in infancy affects cognitive function in adulthood.Design Population based cohort study.Setting Sweden.Participants 3094 men who had received radiation for...

Report of the 115th ENMC workshop: DM2/PROMM and other myotonic dystrophies: 3rd Workshop, 14–16 February 2003, Naarden, The Netherlands

Myotonic dystrophy (DM1, Steinert’s disease) has been known for about 100 years. Its core features are myotonia, muscle weakness, and cataracts [1]. In 1994 another disorder was published with similar core features but lacking the DM1 mutation [2,3]. The name given to this disorder was proximal myotonic myopathy (PROMM, OMIM *160900). The first ENMC workshop on PROMM in 1997 established the clinical criteria for PROMM [4]. Prior to the second ENMC Workshop on PROMM in 2000, a major breakthrough had been accomplished when, in 1998, Ranum and Day [5] described the mapping of a new genetic locus in a large Minnesota family with myotonic dystrophy-like features on chromosome 3q21. This locus was named DM2. As a result, a new nomenclature emerged and the locus for myotonic dystrophy/Steinert’s disease was renamed DM1 [6]. Subsequent work showed that most PROMM families also mapped to the DM2 locus, whereas another smaller group of PROMM families appeared not to be linked to this locus. One separately described family with marked proximal atrophies, called proximal myotonic dystrophy [7], also mapped to the DM2 locus [8], and the workshop adopted the term myotonic dystrophy type 2 (DM2) for all the progressive myotonic multiorgan disorders linked to the DM2 locus. The clinical course of DM2 appeared to be more favourable compared to DM1. Families with DM2 did not have the severe congenital form of illness that occurs in DM1. Abnormalities in the social and cognitive abilities of adults with DM2 were typically mild or absent, and there was no prominent weakness of the facial and bulbar muscles. In DM2 the manual skills largely remained intact, and hypersomnia and mental retardation were not prominent findings. All these characteristic features of DM2 have not changed since the first ENMC Workshop[4]. They are still valid. In the advent of this 3rd workshop on DM2/PROMM, the definitive milestone of research efforts was achieved in 2001 with the identification of the mutation underlying DM2 by Ranum and Day, in collaboration with Ricker [9]. The mutation is a huge (CCTG)n microsatellite repeat expansion in the first intron of the ZNF9 gene and is thus similar to the (CTG)n repeat causing DM1. The aims with this 3rd ENMC Workshop on DM2/PROMM were:

Report of the 84th ENMC Workshop: PROMM (Proximal Myotonic Myopathy) and Other Myotonic Dystrophy-Like Syndromes: 2nd Workshop. 13–15th October, 2000, Loosdrecht, The Netherlands

Report of the 84th ENMC Workshop: PROMM (Proximal Myotonic Myopathy) and Other Myotonic Dystrophy-Like Syndromes: 2nd Workshop. 13–15th October, 2000, Loosdrecht, The Netherlands

Screening Cognitive Abilities in Adults with Developmental Disabilities: Correlations of the K-BIT, PPVT-3, WRAT-3, and CVLT

A screening battery composed of the K-BIT, PPVT-3, WRAT-3, and CVLT was administered to a population of adults with developmental disabilities residing in an intermediate care facility/mental retardation. The cognitive areas investigated were general ability, receptive vocabulary, achievement, and verbal memory. Of primary interest were the correlations between these instruments when administered to this population. The correlations between the K-BIT, PPVT-3, and WRAT-3 were direct and strong, ranging from .72 to .98, whereas the correlations between these tests and the CVLT were direct and moderate, ranging from .45 to .69. These findings support the convergent validity of the K-BIT, PPVT-3, and WRAT-3, and the divergent validity of the CVLT when administered to adults with developmental disabilities.

Memory impairments in adults with neurogenic communication disorders.

Over the past few decades, there has been increasing interest in the nonlinguistic, cognitive abilities of adults with neurogenic communication disorders. In particular, a growing literature has documented deficits in a number of memory functions in this population. The purpose of this article is to summarize that literature and provide an overview of the presence and nature of memory impairments in aphasia, right hemisphere disorders, traumatic brain injury, and dementia. Ways that memory impairments may interact with the communication abilities of individuals with neurogenic communication disorders also are discussed.

Genetic Mediation of the Associations Among Motor and Perceptual Speed and Adult Cognitive Abilities

Quantitative genetic analyses were conducted to determine the genetic mediation of the associations among motor speed, perceptual speed, and cognitive abilities in normal aging. Measures of motor performance, perceptual speed, and cognitive functioning in four domains (crystallized, fluid, spatial, and memory) were available from the Swedish Adoption/Twin Study of Aging. The sample included 206 twin pairs ranging in age from 44 to 82 years. A Motor Speed factor was constructed from 17 timed measures of motor performance. Heritability of Motor Speed was .26 in middle-aged twins and .00 in older twins. Results indicated that genetic variance in cognitive functioning in the middle-aged cohort may be defined by working memory, whereas genetic variance in the older cohort was defined by perceptual speed. Indications of a nonshared environmental component in the association among motor speed, perceptual speed, and spatial abilities suggest possible frontal lobe involvement.

Contribution of age, genes, and environment to the relationship between perceptual speed and cognitive ability.

The aim of this study was to examine genetic influences on cognitive ability in adulthood in the context of the relationship between perceptual speed and cognitive aging. Quantitative genetic analysis of data from the Swedish Adoption/Twin Study of Aging allowed for estimation of the contribution of age, genetic, and environmental effects to the variance in a latent cognitive factor and to the covariance between the cognitive factor and perceptual speed. The sample included 292 pairs of monozygotic and dizygotic twins. both reared together and reared apart, ranging in age from 40 to 84 years. Analysis of components of total variance in the cognitive factor indicated that 90% of the age-related variance in the cognitive factor was shared with perceptual speed and 70% of the genetic variance in the cognitive factor was shared with perceptual speed. The correlation between the speed and cognitive factors was primarily genetically mediated.

Contribution of age, genes, and environment to the relationship between perceptual speed and cognitive ability.

The aim of this study was to examine genetic influences on cognitive ability in adulthood in the context of the relationship between perceptual speed and cognitive aging. Quantitative genetic analysis of data from the Swedish Adoption/Twin Study of Aging allowed for estimation of the contribution of age, genetic, and environmental effects to the variance in a latent cognitive factor and to the covariance between the cognitive factor and perceptual speed. The sample included 292 pairs of monozygotic and dizygotic twins, both reared together and reared apart, ranging in age from 40 to 84 years. Analysis of components of total variance in the cognitive factor indicated that 90% of the age-related variance in the cognitive factor was shared with perceptual speed and 70% of the genetic variance in the cognitive factor was shared with perceptual speed. The correlation between the speed and cognitive factors was primarily genetically mediated.

The 'Severe Impairment Battery': assessing cognitive ability in adults with Down syndrome.

To examine the utility of the 'Severe Impairment Battery' (SIB--Thames Valley Test Company) in assessing cognitive ability of adults with Down syndrome. A within-subject repeated measures design was used to determine test-retest reliability of the SIB and the Vineland Adaptive Behaviour Scales (Interview Edition--Survey Form, 1984) were used to establish SIB criterion validity. Thirty-three adults with Down syndrome (from 152 known to an NHS Trust learning disability service) were selected on the basis of their or their carers' written consent. At the first administration of the SIB with the participant, a staff member completed a Vineland ABS. Thirty days later, the SIB was readministered to the participant. Test-retest reliability of the SIB was high as was criterion validity determined by correlating SIB and Vineland ABS scores. Floor effects were not encountered. The SIB can successfully be used with adults with Down syndrome to assess cognitive functioning over a wide range of ability and may be useful, if used longitudinally, in assessing for deterioration in cognitive functioning associated with dementia. Methodological limitations are discussed.