Associations between polymorphisms in five inflammation‐related genes and cognitive ability in older persons

Several studies have found associations between inflammatory biomarker levels and cognitive ability. This study tested the relationship between polymorphisms in genes that are associated with or encode the biomarkers and cognitive ability and estimated lifetime cognitive change. Data came from the aspirin for asymptomatic atherosclerosis trial (n = 2091, mean age = 67.2 years ). Twelve single nucleotide polymorphisms (SNPs) were genotyped from five genes (IL‐1α, IL‐1β, IL‐6, HNF‐1A and F13A1). Cognition was assessed via administration of a five‐test battery of psychometric tests, which were used to derive a general intelligence factor, g. A vocabulary‐based cognitive test was also administered and adjusted for in the analysis to enable an estimation of lifetime cognitive change. Age‐ and sex‐adjusted analyses yielded one weakly significant association between the IL‐1α rs2856838 SNP and a measure of mental flexibility/processing speed (P = 0.044). Adjustment for the vocabulary‐based scores resulted in a single, significant association between the IL‐1α rs3783546 SNP and a measure of processing speed (P = 0.048). There is little evidence to suggest an association between SNPs in the inflammation‐related genes IL‐1α, IL‐1β, IL‐6, TCF‐1 and F13A1 and cognition in an elderly population of community‐dwelling Scottish citizens.     

Neuropsychological effects of the CSMD1 genome‐wide associated schizophrenia risk variant rs10503253

The single‐nucleotide polymorphism (SNP) rs10503253, located within the CUB and Sushi multiple domains‐1 (CSMD1) gene on 8p23.2, was recently identified as genome‐wide significant for schizophrenia (SZ), but is of unknown function. We investigated the neurocognitive effects of this CSMD1 variant in vivo in patients and healthy participants using behavioral and imaging measures of brain structure and function. We compared carriers and non‐carriers of the risk ‘A’ allele on measures of neuropsychological performance typically impaired in SZ (general cognitive ability, episodic and working memory and attentional control) in independent samples of Irish patients (n = 387) and controls (n = 171) and German patients (205) and controls (n = 533). Across these groups, the risk ‘A’ allele at CSMD1 was associated with deleterious effects across a number of neurocognitive phenotypes. Specifically, the risk allele was associated with poorer performance on neuropsychological measures of general cognitive ability and memory function but not attentional control. These effects, while significant, were subtle, and varied between samples. Consistent with previous evidence suggesting that CSMD1 may be involved in brain mechanisms related to memory and learning, these data appear to reflect the deleterious effects of the identified ‘A’ risk allele on neurocognitive function, possibly as part of the mechanism by which CSMD1 is associated with SZ risk.     

Variants in the 1q21 risk region are associated with a visual endophenotype of autism and schizophrenia

Deficits in sensitivity to visual stimuli of low spatial frequency and high temporal frequency (so‐called frequency‐doubled gratings) have been demonstrated both in schizophrenia and in autism spectrum disorder (ASD). Such basic perceptual functions are ideal candidates for molecular genetic study, because the underlying neural mechanisms are well characterized; but they have sometimes been overlooked in favor of cognitive and neurophysiological endophenotypes, for which neural substrates are often unknown. Here, we report a genome‐wide association study of a basic visual endophenotype associated with psychological disorder. Sensitivity to frequency‐doubled gratings was measured in 1060 healthy young adults, and analyzed for association with genotype using linear regression at 642 758 single nucleotide polymorphism (SNP) markers. A significant association (P = 7.9 × 10^?9) was found with the SNP marker rs1797052, situated in the 5′‐untranslated region of PDZK1; each additional copy of the minor allele was associated with an increase in sensitivity equivalent to more than half a standard deviation. A permutation procedure, which accounts for multiple testing, showed that the association was significant at the α = 0.005 level. The region on chromosome 1q21.1 surrounding PDZK1 is an established susceptibility locus both for schizophrenia and for ASD, mirroring the common association of the visual endophenotype with the two disorders. PDZK1 interacts with N‐methyl‐d ‐aspartate receptors and neuroligins, which have been implicated in the etiologies of schizophrenia and ASD. These findings suggest that perceptual abnormalities observed in two different disorders may be linked by common genetic elements .     

Leisure Activity,Brain β‐amyloid,and Episodic Memory in Adults with Down Syndrome

The present study provided an investigation of associations between leisure activity and early Alzheimer’s disease neuropathology (i.e., brain β‐amyloid) and episodic memory in a sample of 65 adults with Down syndrome (aged 30–53 years), at baseline and follow‐up, approximately three years apart. Findings indicated that leisure activity at baseline was not associated with brain β‐amyloid at baseline or change in brain β‐amyloid from baseline to follow‐up. Greater cognitively stimulating leisure activity at baseline was associated with better episodic memory at baseline, and greater social leisure activity at baseline was associated with less decline in episodic memory from baseline to follow‐up. High (as opposed to low) levels of social and overall leisure activity at baseline moderated the association between increase in brain β‐amyloid and decline in episodic memory, from baseline to follow‐up. Findings suggest that cognitively stimulating and social leisure activity could protect against the effect of Alzheimer’s disease neuropathology on episodic memory in adults with Down syndrome.     

Association between genetic variants of the metabotropic glutamate receptor 3 (GRM3) and cognitive set shifting in healthy individuals

Set‐shifting and maintenance are complex cognitive processes, which are often impaired in schizophrenia. The genetic basis of these processes is poorly understood. We aimed to investigate the association between genetic variants of the metabotropic glutamate receptor 3 (GRM3) and cognitive set‐shifting in healthy individuals. The relationship between 14 selected single nucleotide polymorphisms (SNPs) of the GRM3 gene and cognitive set‐shifting as measured by perseverative errors using the modified card sorting test (MCST) was analysed in a sample of N = 98 young healthy individuals (mean age in years: 22.7 ± 0.19). Results show that SNP rs17676277 is related to the performance on the MCST. Subjects with the TT genotype showed significantly less perseverative errors as compared with the AA (P = 0.025) and AT (P = 0.0005) and combined AA/AT genotypes (P = 0.0005). Haplotype analyses suggest the involvement of various SNPs of the GRM3 gene in perseverative error processing in a dominant model of inheritance. The findings strongly suggest that the genetic variation (rs17676277 and three haplotypes) in the metabotropic GRM3 is related to cognitive set‐shifting in healthy individuals independent of working memory. However, because of a relatively small sample size for a genetic association study, the present results are tentative and require replication.     

Macrophage inhibitory cytokine‐1 is associated with cognitive impairment and predicts cognitive decline – the Sydney Memory and Aging Study

Higher levels of macrophage inhibitory cytokine‐1, also known as growth differentiation factor 15 (MIC‐1/GDF15), are associated with adverse health outcomes and all‐cause mortality. The aim of this study was to examine the relationships between MIC‐1/GDF15 serum levels and global cognition, five cognitive domains, and mild cognitive impairment (MCI), at baseline (Wave 1) and prospectively at 2 years (Wave 2), in nondemented participants aged 70–90 years. Analyses were controlled for age, sex, education, Framingham risk score, history of cerebrovascular accident, acute myocardial infarction, angina, cancer, depression, C‐reactive protein, tumor necrosis factor‐α, interleukins 6 and 12, and apolipoprotein ε4 genotype. Higher MIC‐1/GDF15 levels were significantly associated with lower global cognition at both waves. Cross‐sectional associations were found between MIC‐1/GDF15 and all cognitive domains in Wave 1 (all P < 0.001) and between processing speed, memory, and executive function in Wave 2 (all P < 0.001). Only a trend was found for the prospective analyses, individuals with high MIC‐1/GDF15 at baseline declined in global cognition, executive function, memory, and processing speed. However, when categorizing MIC‐1/GDF15 by tertiles, prospective analyses revealed statistically significant lower memory and executive function in Wave 2 in those in the upper tertile compared with the lower tertile. Receiver operating characteristics (ROC) analysis was used to determine MIC‐1/GDF15 cutoff values associated with cognitive decline and showed that a MIC‐1/GDF15 level exceeding 2764 pg/ml was associated with a 20% chance of decline from normal to MCI or dementia. In summary, MIC‐1/GDF15 levels are associated with cognitive performance and cognitive decline. Further research is required to determine the pathophysiology of this relationship.     

COMT rs4680 Met is not always the ‘smart allele’: Val allele is associated with better working memory and larger hippocampal volume in healthy Chinese

Catechol‐O‐methyltransferase (COMT) Val158Met (rs4680) polymorphism plays a crucial role in regulating brain dopamine level. Converging evidence from Caucasian samples showed that, compared with rs4680 Val allele, the Met allele was linked to lower COMT activity, which in turn was linked to better cognitive performance such as working memory (WM) and to a larger hippocampus (a brain region important for WM). However, some behavioral studies have shown that the function of rs4680 appears to vary across different ethnic groups, with Chinese subjects showing an opposite pattern as that for Caucasians (i.e. the Val allele is linked to better cognitive functions related to WM in Chinese). Using a sample of healthy Han Chinese college students (ages from 19 to 21 years), this study investigated the association of COMT Val158Met genotype with behavioral data on a two‐back WM task (n = 443, 189M/254F) and T1 MRI data (n = 320, 134M/186F). Results showed that, compared to the Met allele, the Val allele was associated with larger hippocampal volume (the right hippocampus: β = ?0.118, t = ?2.367, P = 0.019, and the left hippocampus: β = ?0.099, t = ?1.949, P = 0.052) and better WM performance (β = ?0.110, t = ?2.315, P = 0.021). These results add to the growing literature on differentiated effects of COMT rs4680 polymorphism on WM across populations and offer a brain structural mechanism for such population‐specific genetic effects.     

Performance in working memory and attentional control is associated with the rs2180619 SNP in the CNR1 gene

Individual differences in cognitive performance are partly dependent, on genetic polymporhisms. One of the single‐nucleotide polymorphisms (SNP) of the CNR1 gene, which codes for cannabinoid receptor 1 (CB1R), is the rs2180619, located in a regulatory region of this gene (6q14–q15). The alleles of the rs2180619 are A > G; the G allele has been associated with addiction and high levels of anxiety (when the G allele interacts with the SS genotype of the 5‐HTTLPR gene). However, GG genotype is observed also in healthy subjects. Considering G allele as risk for ‘psychopathological conditions’, it is possible that GG healthy subjects do not be addicted or anxious, but would have reduced performance, compared to AA subjects, in attentional control and working memory processing. One hundred and sixty‐four healthy young Mexican‐Mestizo subjects (100 women and 64, men; mean age: 22.86 years, SD=2.72) participated in this study, solving a task where attentional control and working memory were required. GG subjects, compared to AA subjects showed: (1) a general lower performance in the task (P = 0.02); (2) lower performance only when a high load of information was held in working memory (P = 0.02); and (3) a higher vulnerability to distractors (P = 0.03). Our results suggest that, although the performance of GG subjects was at normal levels, a lower efficiency of the endocannabinoid system, probably due to a lowered expression of CB1R, produced a reduction in the performance of these subjects when attentional control and working memory processing is challenged .     

Relationship between Auditory and Cognitive Abilities in Older Adults

Objective

The objective was to evaluate the association of peripheral and central hearing abilities with cognitive function in older adults.

Methods

Recruited from epidemiological studies of aging and cognition at the Rush Alzheimer’s Disease Center, participants were a community-dwelling cohort of older adults (range 63–98 years) without diagnosis of dementia. The cohort contained roughly equal numbers of Black (n=61) and White (n=63) subjects with groups similar in terms of age, gender, and years of education. Auditory abilities were measured with pure-tone audiometry, speech-in-noise perception, and discrimination thresholds for both static and dynamic spectral patterns. Cognitive performance was evaluated with a 12-test battery assessing episodic, semantic, and working memory, perceptual speed, and visuospatial abilities.

Results

Among the auditory measures, only the static and dynamic spectral-pattern discrimination thresholds were associated with cognitive performance in a regression model that included the demographic covariates race, age, gender, and years of education. Subsequent analysis indicated substantial shared variance among the covariates race and both measures of spectral-pattern discrimination in accounting for cognitive performance. Among cognitive measures, working memory and visuospatial abilities showed the strongest interrelationship to spectral-pattern discrimination performance.

Conclusions

For a cohort of older adults without diagnosis of dementia, neither hearing thresholds nor speech-in-noise ability showed significant association with a summary measure of global cognition. In contrast, the two auditory metrics of spectral-pattern discrimination ability significantly contributed to a regression model prediction of cognitive performance, demonstrating association of central auditory ability to cognitive status using auditory metrics that avoided the confounding effect of speech materials.     

White Matter Integrity Supports BOLD Signal Variability and Cognitive Performance in the Aging Human Brain

Decline in cognitive performance in old age is linked to both suboptimal neural processing in grey matter (GM) and reduced integrity of white matter (WM), but the whole-brain structure-function-cognition associations remain poorly understood. Here we apply a novel measure of GM processing–moment-to-moment variability in the blood oxygenation level-dependent signal (SD_BOLD)—to study the associations between GM function during resting state, performance on four main cognitive domains (i.e., fluid intelligence, perceptual speed, episodic memory, vocabulary), and WM microstructural integrity in 91 healthy older adults (aged 60-80 years). We modeled the relations between whole-GM SD_BOLD with cognitive performance using multivariate partial least squares analysis. We found that greater SD_BOLD was associated with better fluid abilities and memory. Most of regions showing behaviorally relevant SD_BOLD (e.g., precuneus and insula) were localized to inter- or intra-network “hubs” that connect and integrate segregated functional domains in the brain. Our results suggest that optimal dynamic range of neural processing in hub regions may support cognitive operations that specifically rely on the most flexible neural processing and complex cross-talk between different brain networks. Finally, we demonstrated that older adults with greater WM integrity in all major WM tracts had also greater SD_BOLD and better performance on tests of memory and fluid abilities. We conclude that SD_BOLD is a promising functional neural correlate of individual differences in cognition in healthy older adults and is supported by overall WM integrity.     

Polymorphisms associated with normal memory variation also affect memory impairment in schizophrenia

Neurocognitive dysfunction is a core feature of schizophrenia with particularly prominent deficits in verbal episodic memory. The molecular basis of this memory impairment is poorly understood and its relatedness to normal variation in memory performance is unclear. In this study, we explore, in a sample of cognitively impaired schizophrenia patients, the role of polymorphisms in seven genes recently reported to modulate episodic memory in normal subjects. Three polymorphisms (GRIN2B rs220599, GRM3 rs2189814 and PRKCA rs8074995) were associated with episodic verbal memory in both control and patients with cognitive deficit, but not in cognitively spared patients or the pooled schizophrenia sample. GRM3 and PRKCA acted in opposite directions in patients compared to controls, possibly reflecting an abnormal brain milieu and/or adverse environmental effects in schizophrenia. The encoded proteins balance glutamate signalling vs. excitotoxicity in complex interactions involving the excitatory amino acid transporter 2 (EAAT2), implicated in the dysfunctional glutamatergic signalling in schizophrenia. Double carrier status of the GRM3 and PRKCA minor alleles was associated with lower memory test scores and with increased risk of schizophrenia. Single nucleotide polymorphism (SNP) rs8074995 lies within the PRKCA region spanned by a rare haplotype associated with schizophrenia in a recent UK study and provides further evidence of PRKCA contribution to memory impairment and susceptibility to schizophrenia. Our study supports the utility of parsing the broad phenotype of schizophrenia into component cognitive endophenotypes that reduce heterogeneity and enable the capture of potentially important genetic associations.     

Association between the oxytocin receptor (OXTR) gene and children's social cognition at 18 months

At 18 months, children engage in a variety of social behaviors that reflect their nascent ability to understand the intentions of other people (e.g. joint attention, empathy, cooperation and self‐recognition). Although numerous contextual factors have been shown to predict social cognition in young children, the genetic underpinnings of social‐cognitive traits has been understudied in this age group. Owing to the known effects of oxytocin on adult social cognition and psychopathology, this study hypothesized that variability in the oxytocin receptor gene (OXTR) would be associated with social cognition in children at 18 months. Participants consisted of 350 children (182 males; 168 females) who were part of an ongoing longitudinal study that aimed to assess environmental and genetic contributions to children's cognitive and socio‐emotional functioning. At 18 months, social cognition was measured using previously validated and developmentally sensitive tasks assessing children's joint attention, empathy, cooperation and self‐recognition. Five potentially functional OXTR variants were genotyped: rs1042778, rs2254298, rs11131149, rs237897 and rs237899. A family‐based association design was used to control for population admixture and stratification, and additional non‐genomic covariates were controlled. Results showed that variability in rs11131149 was significantly associated with social cognition (P = 0.009), with more copies of the major allele related to higher social cognition, and more copies of the minor (risk) allele associated with lower social cognition. A haplotype consisting of rs11131149–rs2254298 was also associated with social cognition (P = 0.020). Implications for normative and pathological development are discussed, and key areas for future research are proposed.     

Genome‐wide Association Study and Follow‐up Analysis of Adiposity Traits in Hispanic Americans: The IRAS Family Study

We investigated candidate genomic regions associated with computed tomography (CT)–derived measures of adiposity in Hispanics from the Insulin Resistance Atherosclerosis Study Family Study (IRASFS). In 1,190 Hispanic individuals from 92 families 3 from the San Luis Valley, Colorado and San Antonio, Texas, we measured CT‐derived visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), and visceral:subcutaneous ratio (VSR). A genome‐wide association study (GWAS) was completed using the Illumina HumanHap 300 BeadChip (～317K single‐nucleotide polymorphisms (SNPs)) in 229 individuals from the San Antonio site (stage 1). In total, 297 SNPs with evidence for association with VAT, SAT, or VSR, adjusting for age and sex (P < 0.001), were genotyped in the remaining 961 Hispanic samples. The entire Hispanic cohort (n = 1,190) was then tested for association, adjusting for age, sex, site of recruitment, and admixture estimates (stage 2). In stage 3, additional SNPs were genotyped in four genic regions showing evidence of association in stage 2. Several SNPs were associated in the GWAS (P < 1 × 10^?5) and were confirmed to be significantly associated in the entire Hispanic cohort (P < 0.01), including: rs7543757 for VAT, rs4754373 and rs11212913 for SAT, and rs4541696 and rs4134351 for VSR. Numerous SNPs were associated with multiple adiposity phenotypes. Targeted analysis of four genes whose SNPs were significant in stage 2 suggests candidate genes for influencing the distribution (RGS6) and amount of adiposity (NGEF). Several candidate loci, including RGS6 and NGEF, are associated with CT‐derived adipose fat measures in Hispanic Americans in a three‐stage genetic association study.     

Isoform‐specific effects of apolipoprotein E on cognitive performance in targeted‐replacement mice overexpressing human APP

The ε4 allele of apolipoprotein E (apoE4) is the predominant genetic risk factor for late‐onset Alzheimer's disease (AD) and is also implicated in cognitive deficits associated with normal aging. The biological mechanisms by which APOE genotype affects cognitive processes or AD pathogenesis remain unclear, but interactions of apoE with amyloid β peptide (Aβ) are thought to play an important role in mediating apoE's isoform‐specific effects on brain function. Here, we investigated the potential isoform‐dependent effects of apoE on behavioral and cognitive performance in human apoE3 and apoE4 targeted‐replacement (TR) mice that also overexpress the human amyloid precursor protein (APP). Beginning at 6–7 months of age, female APP‐Yac/apoE3‐TR (‘poE3’) and APP‐Yac/apoE4‐TR (‘poE4’) mice were tested on a battery of tests to evaluate basic sensorimotor functioning, spatial working memory, spatial recognition, episodic‐like memory and attentional processing. Compared with apoE3 mice, a generalized reduction in locomotor activity was observed in apoE4 mice. Moderate, but significant, cognitive impairments were also detected in apoE4 mice in the novel object‐location preference task, the contextual fear conditioning test, and a two‐choice visual discrimination/detection test, however spontaneous alternation performance in the Y‐maze was spared. These results offer additional support for the negative impact of apoE4 on both memory and attention and further suggest that APP‐Yac/apoE‐TR mice provide a novel and useful model for investigating the role of apoE in mediating susceptibility to cognitive decline.     

Predictors and correlates of edentulism in the healthy old people in Edinburgh (HOPE) study

Objectives: To determine the extent to which correlates of edentulism are explained by an association between tooth loss and cognitive ability. Methods: Participants in the Healthy Old People in Edinburgh (HOPE) study aged 70 or more at baseline were assessed and health, cognitive, socio‐economic and socio‐environmental data collected on four consecutive occasions. It was noted whether the participant had any retained teeth and if not, the age when the last tooth was lost. Prior determinants of edentulism were investigated with binary logistic regression models. At the 9‐year follow‐up, associations with edentulism were examined using general linear models with edentulism as an independent factor. Results: 201 participants were adequately tested, of whom 104 (51.7%) were edentulous. A logistic regression model that considered age, sex, education, social class, deprivation index of residence, objective distance from dentist, participant’s estimate of distance from dentist and NART‐estimated IQ (NARTIQ) found age (p = 0.032), occupational class (p = 0.019) and NARTIQ (p = 0.027) as significant predictors of edentulism. Cox’s proportional hazards modelling found only NARTIQ (p = 0.050) to be correlated. Being edentulous was associated with poorer respiratory function but not hand grip strength (p = 0.23). Edentulous participants had lower self esteem scores (p = 0.020) and poorer dietary assessment scores (p = 0.028). Being edentulous was also associated with significantly lower mean scores on all cognitive testing, although these associations became non‐significant after adjustment for NARTIQ and age. Conclusions: In healthy older people, edentulism is associated with relative impairment of cognitive ability, although this association is explained by the fact that lower original intelligence predisposes to edentulism and poorer performance on cognitive tests in old age. Once original intelligence is adjusted for, tooth loss is not related to cognitive ability. Tooth loss is, however, associated with poorer status across a wide range of health measures: physical health, nutrition, disability and self‐esteem. Establishing the degree to which these health outcomes are causally related to edentulism could usefully be factored into cost–benefit analyses of programmes designed to prevent tooth loss.     

CHRNA5 variants moderate the effect of nicotine deprivation on a neural index of cognitive control

Individuals with reduced attention and memory cognitive control‐related processes may be motivated to smoke as a result of the cognitive enhancing effects of nicotine. Further, nicotine deprivation‐induced reductions in cognitive control may negatively reinforce smoking. Minor allele carriers at rs16969968 in the nicotinic acetylcholine receptor α5 subunit gene (CHRNA5) have been shown to exhibit both reduced cognitive control and greater nicotine dependence. It is therefore of interest to see if variants in this gene moderate the influence of nicotine deprivation on cognitive control. P3b and P3a components of the event‐related brain potential waveform evoked by a three‐stimulus visual oddball task are widely viewed as positive indices of cognitive control‐related processes. We tested the hypothesis that individuals possessing at least one minor allele at rs16969968 in CHRNA5 would show greater nicotine deprivation‐induced reductions in P3b and P3a amplitude. The sample included 72 non‐Hispanic, Caucasian heavy smokers (54 men and 18 women) with a mean age of 36.11 years (SD = 11.57). Participants completed the visual oddball task during counterbalanced nicotine and placebo smoking sessions. Findings indicated that rs16969968 status did not moderate nicotine effects on P3b or P3a, whereas variation in other CHRNA5 polymorphisms, which are not as well characterized and are not in linkage disequilibrium with rs16969968, predicted nicotine deprivation‐induced reduction of P3a amplitude: rs588765 (F_1,68 = 7.74, P = 0.007) and rs17408276 (F_1,67 = 7.34, P = 0.009). Findings are interpreted in the context of vulnerability alleles that may predict nicotine effects on cognitive control.     

Glutamate Receptor 6 Gene (<Emphasis Type="Italic">GluR6</Emphasis> or <Emphasis Type="Italic">GRIK2</Emphasis>) Polymorphisms in the Indian Population: A Genetic Association Study on Autism Spectrum Disorder

Autism is a neurodevelopmental disorder with early manifestation. It is a multifactorial disorder and several susceptible chromosomal regions for autism are identified through genome scan studies. The gene coding for glutamate receptor 6 (GluR6 or GRIK2) has been suggested as a candidate gene for autism based on its localization in the autism specific region on chromosome 6q21 and the involvement of receptor protein in cognitive functions like learning and memory. Despite its importance, so far no studies have been carried out on possible involvement of GluR6 with autism in the Indian population. Therefore in the present study, we have performed genetic analysis of three markers of GluR6 (SNP1: rs2227281, SNP2: rs2227283, SNP3: rs2235076) for possible association with autism through population, and family-based (TDT and HHRR) approaches. DSM-IV criteria and CARS/ADI-R have been utilized for diagnosis. Genotyping analysis for the SNPs has been carried out in 101 probands with autism spectrum disorder, 180 parents and 152 controls from different regions of India. Since the minor allele frequency of SNP3 was too low, the association studies have been carried out only for SNP1 and SNP2. Even though two earlier studies have shown association of these markers with autism, the present case–control and TDT, as well as HHRR analyses have not demonstrated any biased transmission of alleles or haplotypes to the affected offspring. Thus our results suggest that these markers of GluR6 are unlikely to be associated with autism in the Indian population.     

Deterioration in Motor Function Over Time in Older Adults With Type 2 Diabetes is Associated with Accelerated Cognitive Decline

Objective: Type 2 diabetes (T2D) is associated with motor impairments and a higher dementia risk. The relationships of motor decline with cognitive decline in T2D older adults has rarely been studied. Using data from the Israel Diabetes and Cognitive Decline study (N = 892), we examined associations of decline in motor function with cognitive decline over a 54-month period.Methods: Motor function measures were strength (handgrip) and gait speed (time to walk 3 m). Participants completed a neuropsychologic battery of 13 tests transformed into z-scores, summarized into 4 cognitive domains: episodic memory, attention/working memory, executive functions, and language/semantic categorization. The average of the 4 domains’ z-scores defined global cognition. Motor and cognitive functions were assessed in 18-months intervals. A random coefficients model delineated longitudinal relationships of cognitive decline with baseline and change from baseline in motor function, adjusting for sociodemographic, cardiovascular, and T2D-related covariates.Results: Slower baseline gait speed levels were significantly associated with more rapid decline in global cognition (P = .004), language/semantic categorization (P = .006) and episodic memory (P = .029). Greater decline over time in gait speed was associated with an accelerated rate of decline in global cognition (P = .050), attention/working memory (P = .047) and language/semantic categorization (P<.001). Baseline strength levels were not associated with cognitive decline but the rate of declining strength was associated with an accelerated decline in executive functions (P = .025) and language/semantic categorization (P = .006).Conclusion: In T2D older adults, the rate of decline in motor function, beyond baseline levels, was associated with accelerated cognitive decline, suggesting that cognitive and motor decline share common neuropathologic mechanisms in T2D.     

The Implications of Body Fat Mass and Fat Distribution for Cognitive Function in Elderly Women

Objective: To investigate how body fat mass, an established source of endogenous estrogen after menopause, influences cognitive impairment in elderly women. Research Methods and Procedures: Study participants were 5607 generally healthy postmenopausal women with mean age of 63.8 years at baseline followed for an average of 7.3 years. Cognitive function assessed at follow‐up using the short Blessed test was related to baseline body weight, the yearly change in weight, and follow‐up measures of body fat depots assessed by DXA. Cognitive function was also related to various surrogates of lifetime estrogen exposure. Results: Women with the worst cognitive performance (score ≥ 9) at follow‐up were the ones who lost the most body weight and revealed the lowest central fat mass (CFM). The association of weight loss with worse cognitive performance was apparent across all age groups except for those more than 80 years old. In the multivariate logistic model, the risk of cognitive impairment was 18% lower in women in the second quartile of CFM (p = 0.14), 32% lower in the third (p = 0.01), and 48% lower in the fourth (p < 0.001) compared with those in the first quartile. CFM showed significant correlation with the simultaneously measured serum estradiol (r = 0.25; p < 0.001). Cognitive score showed an inverse linear relationship with the duration of reproductive period and bone mineral density assessed at follow‐up. Discussion: These findings argue for a protective association of body fat mass with cognitive impairment in elderly women. This association seems to involve a more prominent exposure to endogenous estrogens.