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Several judgment and decision-making tasks are assumed to involve memory functions, but significant knowledge gaps on the memory processes underlying these tasks remain. In a study on 568 adults between 25 and 80 years of age, hypotheses were tested on the specific relationships between individual differences in working memory, episodic memory, and semantic memory, respectively, and 6 main components of decision-making competence. In line with the hypotheses, working memory was positively related with the more cognitively demanding tasks (Resistance to Framing, Applying Decision Rules, and Under/Overconfidence), whereas episodic memory was positively associated with a more experience-based judgment task (Recognizing Social Norms). Furthermore, semantic memory was positively related with 2 more knowledge-based decision-making tasks (Consistency in Risk Perception and Resistance to Sunk Costs). Finally, the age-related decline observed in some of the decision-making tasks was (partially or totally) mediated by the age-related decline in working memory or episodic memory. These findings are discussed in relation to the functional roles fulfilled by different memory processes in judgment and decision-making tasks.

Objectives To determine whether dementia could explain the association between poor olfactory performance and mortality risk within a decade-long follow-up period. Design Prospective cohort study. Setting Betula Study, Umeå, Sweden. Participants A population-based sample of adult participants without dementia at baseline aged 40 to 90 (N = 1,774). Measurements Olfactory performance using the Scandinavian Odor-Identification Test ( SOIT) and self-reported olfactory function; several social, cognitive, and medical risk factors at baseline; and incident dementia during the following decade. Results Within the 10-year follow-up, 411 of 1,774 (23.2%) participants had died. In a Cox model, the association between higher SOIT score and lower mortality was significant (hazard ratio ( HR) = 0.74 per point interval, 95% confidence interval ( CI) = 0.71-0.77, P < .001). The effect was attenuated, but remained significant, after controlling for age, sex, education, and health-related and cognitive variables ( HR = 0.92, 95% CI = 0.87-0.97, P = .001). The association between SOIT score and mortality was retained after controlling for dementia conversion before death ( HR = 0.92, 95% CI = 0.87-0.97, P = .001). Similar results were obtained for self-reported olfactory dysfunction. Conclusion Poor odor identification and poor self-reported olfactory function are associated with greater likelihood of future mortality. Dementia does not attenuate the association between olfactory loss and mortality, suggesting that olfactory loss might mark deteriorating health, irrespective of dementia. [ABSTRACT FROM AUTHOR]

BACKGROUND: Exposure to ambient air pollution is suspected to cause cognitive effects, but a prospective cohort is needed to study exposure to air pollution at the home address and the incidence of dementia. OBJECTIVES: We aimed to assess the association between long-term exposure to traffic-related air pollution and dementia incidence in a major city in northern Sweden. METHODS: Data on dementia incidence over a 15-year period were obtained from the longitudinal Betula study. Traffic air pollution exposure was assessed using a land-use regression model with a spatial resolution of 50 m x 50 m. Annual mean nitrogen oxide levels at the residential address of the participants at baseline (the start of follow-up) were used as markers for long-term exposure to air pollution. RESULTS: Out of 1,806 participants at baseline, 191 were diagnosed with Alzheimer's disease during follow-up, and 111 were diagnosed with vascular dementia. Participants in the group with the highest exposure were more likely than those in the group with the lowest exposure to be diagnosed with dementia (Alzheimer's disease or vascular dementia), with a hazard ratio (HR) of 1.43 (95% CI: 0.998, 2.05 for the highest vs. the lowest quartile). The estimates were similar for Alzheimer's disease (HR 1.38) and vascular dementia (HR 1.47). The HR for dementia associated with the third quartile versus the lowest quartile was 1.48 (95% CI: 1.03, 2.11). A subanalysis that excluded a younger sample that had been retested after only 5 years of follow-up suggested stronger associations with exposure than were present in the full cohort (HR = 1.71; 95% CI: 1.08, 2.73 for the highest vs. the lowest quartile). CONCLUSIONS: If the associations we observed are causal, then air pollution from traffic might be an important risk factor for vascular dementia and Alzheimer's disease. [ABSTRACT FROM AUTHOR]

Testing one's memory of previously studied information reduces the rate of forgetting, compared to restudy. However, little is known about how this direct testing effect applies to action phrases (e.g., 'wash the car') - a learning material relevant to everyday memory. As action phrases consist of two different components, a verb (e.g., 'wash') and a noun (e.g., 'car'), testing can either be implemented as noun-cued recall of verbs or verb-cued recall of nouns, which may differently affect later memory performance. In the present study, we investigated the effect of testing for these two recall types, using verbally encoded action phrases as learning materials. Results showed that repeated study-test practice, compared to repeated study-restudy practice, decreased the forgetting rate across 1 week to a similar degree for both noun-cued and verb-cued recall types. However, noun-cued recall of verbs initiated more new subsequent learning during the first restudy, compared to verb-cued recall of nouns. The study provides evidence that testing has benefits on both subsequent restudy and long-term retention of action-relevant materials, but that these benefits are differently expressed with testing via noun-cued versus verb-cued recall. [ABSTRACT FROM AUTHOR]

We investigated the factorial structure of the Perceived Stress Questionnaire ( PSQ-recent; Levenstein, Prantera, Varvo et al., 1993) in a large ( N = 1516; 35-95 years) population-based Swedish sample (Nilsson, Adolfsson, Bäckman et al., 2004; Nilsson, Bäckman, Erngrund et al., 1997). Exploratory principal components analysis ( PCA) was conducted on a first, randomly drawn subsample ( n = 506). Next, the model based on the PCA was tested in a second sample ( n = 505). Finally, a third sample ( n = 505) was used to cross-validate the model. Five components were extracted in the PCA (eigenvalue > 1) and labeled 'Demands,' 'Worries/Tension,' 'Lack of joy,' 'Conflict,' and 'Fatigue,' respectively. Twenty-one out of the 30 original PSQ items were retained in a confirmatory factor analysis ( CFA) model that included the five (first-order) factors and, additionally, a general (second-order) stress factor, not considered in prior models. The model showed reasonable goodness of fit [χ2(184) = 511.2, p < 0.001; CFI = 0.904; RMSEA = 0.059; and SRMR = 0.063]. Multigroup confirmatory factor analyses supported the validity of the established model. The results are discussed in relation to prior investigations of the factorial structure of the PSQ. [ABSTRACT FROM AUTHOR]

The present study examined the relationships between different types of social and cognitive activities and different types of episodic and semantic memory. A total of 794 adult men and women from five age cohorts (aged 65-85 at baseline), participating in the longitudinal Betula project on ageing, memory, and health, were included in the study. The participants were studied over 10 years (1995-2005) in three waves. Recognition and recall were used as episodic memory tasks, and knowledge and verbal fluency as semantic memory tasks. The results, after controlling for age, gender, education, and some diseases, including heart disease and hypertension, as covariates, showed unidirectional effects of social activity on episodic memory on all test occasions (β = .10). Also, episodic memory predicted change in cognitive activity for all test waves (β = .21-.22). Findings suggest that social activity can be seen as protective factor against memory decline. It also seems that episodic memory performance is a predictor of cognitive activity in old people. However, the opposite direction does not hold true. [ABSTRACT FROM AUTHOR]

Objectives. The aim of this study was to investigate whether leisure activity is associated with incident dementia in an older sample. Method. We examined a sample of 1,475 elderly (≥ 65 years) who were dementia free at baseline over a follow-up period of up to 15 years. In addition to analyses involving the total time period, separate analyses of three time periods were performed, 1–5, 6–10, and 11–15 years, following baseline measurement of leisure activity. Results. After controlling for a variety of potential confounders, analyses of data for the total time period revealed that higher levels of “Total activity” and “Social activity,” but not “Mental activity,” were associated with decreased risk of dementia. However, analyses of the separate time periods showed that this association was only significant in the first time period, 1–5 years after baseline. Discussion. The results from this study provide little support for the hypothesis that frequent engagement in leisure activities among elderly serve to protect against dementia diseases across a longer time frame. The finding of a relationship for the first time period, 1–5 years after baseline, could indicate short-term protective effects but could also reflect reverse causality. [ABSTRACT FROM PUBLISHER]

Background: leukocyte telomere length (TL) is considered a marker of biological aging. Several studies have investigated the link between leukocyte TL and aging-associated functional attributes of the brain, but no prior study has investigated whether TL can be linked to brain atrophy and white matter hyperintensities (WMHs); two prominent structural manifestations of brain aging.Methods: we investigated whether leukocyte TL was related to brain atrophy and WMHs in a sample of 102 non-demented individuals aged 64–75 years.Results: shorter TL was related to greater degree of subcortical atrophy (β = −0.217, P = 0.034), but not to cortical atrophy. Furthermore, TL was 371 bp shorter (P = 0.041) in participants exhibiting subcortical WMHs, and 552 bp shorter (P = 0.009) in older participants exhibiting periventricular WMHs.Conclusion: this study provides the first evidence of leukocyte TL being associated with cerebral subcortical atrophy and WMHs, lending further support to the concept of TL as a marker of biological aging, and in particular that of the aging brain. [ABSTRACT FROM AUTHOR]

Mousavi-Nasab, S.-M.-H., Kormi-Nouri, R., Sundström, A. & Nilsson, L.-G. (2011). The effects of marital status on episodic and semantic memory in healthy middle-aged and old individuals. Scandinavian Journal of Psychology 53, 1-8. The present study examined the influences of marital status on different episodic and semantic memory tasks. A total of 1882 adult men and women participated in a longitudinal project (Betula) on memory, health and aging. The participants were grouped into two age cohorts, 35-60 and 65-85, and studied over a period of 5 years. Episodic memory tasks concerned recognition and recall, whereas semantic memory tasks concerned knowledge and fluency. The results showed, after controlling for education, some diseases, chronological age and leisure activity as covariates, that there were significant differences between married and single individuals in episodic memory, but not in semantic memory. Married people showed significantly better memory performances than singles in both subsystems of episodic memory, that is, recall and recognition. Also, the rate of decline in episodic memory was significantly larger for singles and widowed than other groups over the 5-year time period in both age groups. The findings demonstrate that the positive relation found between marriage and health can be extended to the relation between marriage and cognitive performance. This effect might be explained by the role played by cognitive stimulation in memory and cognition. [ABSTRACT FROM AUTHOR]

Ceulemans S, De Zutter S, Heyrman L, Norrback K-F, Nordin A, Nilsson L-G, Adolfsson R, Del-Favero J, Claes S. Evidence for the involvement of the glucocorticoid receptor gene in bipolar disorder in an isolated northern Swedish population. Bipolar Disord 2011: 13: 614-623. © 2011 The Authors. Journal compilation © 2011 John Wiley & Sons A/S. Objectives: Dysfunction of the hypothalamus-pituitary-adrenal (HPA) axis is one of the most consistent findings in the pathophysiology of mood disorders. The potential role of genes related to HPA axis function has been investigated extensively in major depression. However, in bipolar disorder (BPD) such studies are scarce. We performed a systematic HapMap-based association study of six genes crucial for HPA axis function in relation to BPD. Methods: Haplotype tagging single nucleotide polymorphisms (htSNPs) were selected in order to identify all haplotypes with a frequency of more than 1% in the genes encoding the glucocorticoid receptor (GR), mineralocorticoid receptor (MR), corticotrophin releasing hormone receptor 1 (CRH-R1) and 2 (CRH-R2), CRH binding protein (CRH-BP), and FK binding protein 5 (FKBP5). This resulted in a total selection of 225 SNPs that were genotyped and analyzed in 309 BPD patients and 364 matched control individuals all originating from an isolated northern Swedish population. Results: Consistent evidence for an association with BPD was found for NR3C1, the gene encoding GR. Almost all SNPs in two adjacent haplotype blocks contributed to the positive signal, comprised of significant single marker, sliding window, and haplotype-specific p-values. All these results point to a moderately frequent (10-15%) susceptibility haplotype covering the entire coding region and 3′ untranslated region (UTR) of NR3C1. Conclusions: This study contributes to the growing evidence for a role of the glucocorticoid receptor gene ( NR3C1) in vulnerability to mood disorders, and BPD in particular, and warrants further in vitro investigation of the at-risk haplotypes with respect to disease etiology. However, this association might be restricted to this specific population, as it is observed in a rather small sample from an isolated population without replication, and data from large meta-analyses for genome-wide association studies in BPD do not show the GR as a very strong candidate. [ABSTRACT FROM AUTHOR]

Lekander, M., von Essen, J., Schultzberg, M., Andreasson, A. N., Garlind, A., Hansson, L.-O. & Nilsson, L.-G. (2011). Cytokines and memory across the mature life span of women. Scandinavian Journal of Psychology 52, 229-235. Increasing evidence suggests a role of the immune system in modulation of cognition, but details on affected memory systems are largely lacking. We therefore aimed to study the relation between selected cytokines and subsets of memory, and the impact of age in these relations. From a random population-based sample (the Betula Prospective Cohort Study), 298 women (age 45-90) were studied in terms of episodic recall and recognition, semantic fluency and knowledge, and prospective memory. Circulating cytokines of relevance for cognition and aging were measured with ELISA. Levels of interleukin (IL)-6 and sIL-2R were significantly and negatively associated with most cognitive variables, while the opposite was true for IL-1β. Age shared substantial variance with both cytokines and memory, and turned most correlations non-significant when controlled for together with education, BMI and presence of disease. Interactions between age and cytokines were further analyzed in multiple regressions. For IL-6, significant negative interactions with age were found for semantic fluency ( p < 0.05) and prospective memory ( p < 0.01), and for sIL-2R in predicting semantic knowledge ( p < 0.05), indicating an increased negative impact of these cytokines on memory with increasing age. In conclusion, the study indicates a relation between cytokines and memory that appears to be largely mediated by age, and supports the suggestion that cytokine dysregulation with higher age may interact with cognitive aging. [ABSTRACT FROM AUTHOR]

Vestergren, P., Rönnlund, M., Nyberg, L. & Nilsson, L.-G. (2011). Development of the Cognitive Dysfunction Questionnaire (CDQ) in a population based sample. Scandinavian Journal of Psychology 52, 218-228. The study reports on the development of a questionnaire for assessment of adult cognitive dysfunction (CDQ). Participants in a population-based sample (65 ± 15 years, N = 370) responded to a 90-item pilot version covering multiple aspects of memory/cognition. Based on exploratory principal components analyses and correlations with criterion measures of cognitive functioning (MMSE, Block Design, semantic/episodic memory), 20 items loading on 6 components were selected for the final version of the questionnaire. Cronbach's α for the total score was 0.90. There was evidence of construct validity as judged by correlations between CDQ scores, objective cognitive measures, and a subjective memory measure (PRMQ). Discriminant validity was demonstrated by a low and non-significant correlation with depressive symptoms. Further evidence of construct validity was provided by correlations with age and educational attainment. In conclusion, the CDQ is promising as a self-rating screening tool for cognitive dysfunction, and will be the subject of further development and validation. [ABSTRACT FROM AUTHOR]

Rationale: To allow for interdisciplinary research on the relations between socioeconomic conditions and health in the ageing population, a new anonymized longitudinal database — the Linnaeus Database — has been developed at the Centre for Population Studies at Umeå University. This paper presents the database and its research potential. Design: Using the Swedish personal numbers the researchers have, in collaboration with Statistics Sweden and the National Board for Health and Welfare, linked individual records from Swedish register data on death causes, hospitalization and various socioeconomic conditions with two databases — Betula and VIP (Västerbottens Intervention Programme) — previously developed by the researchers at Umeå University. Whereas Betula includes rich information about e.g. cognitive functions, VIP contains information about e.g. lifestyle and health indicators. Population and sample size: The Linnaeus Database includes annually updated socioeconomic information from Statistics Sweden registers for all registered residents of Sweden for the period 1990 to 2006, in total 12,066,478. The information from the Betula includes 4,500 participants from the city of Umeå and VIP includes data for almost 90,000 participants. Both datasets include cross-sectional as well as longitudinal information. Potential: Due to the coverage and rich information, the Linnaeus Database allows for a variety of longitudinal studies on the relations between, for instance, socioeconomic conditions, health, lifestyle, cognition, family networks, migration and working conditions in ageing cohorts. Conclusions: By joining various datasets developed in different disciplinary traditions new possibilities for interdisciplinary research on ageing emerge. [ABSTRACT FROM PUBLISHER]

OBJECTIVE--Patients with type 2 diabetes have an increased risk of a reduction in cognitive function. We investigated the hypothesis that plasma glucose is associated with a reduction in episodic and/or semantic memory already in nondiabetic subjects. RESEARCH DESIGN AND METHODS--We linked two large population-based datasets in Sweden: the Betula study, in which a random sample from the population aged 35-85 years was investigated for cognitive function, including episodic and semantic memory; and the Västerbotten Intervention Program, a health survey with subjects aged 40, 50, and 60 years, that includes measuring of fasting and 2-h plasma glucose, along with other risk factors for diabetes and cardiovascular disease. We identified 411 (179 men and 232 women, mean age 50.6 ± 8.0 years) nondiabetic subjects, free from dementia, who had participated in the two surveys within 6 months. RESULTS--Women had better episodic (score 7.37 ± 1.42) and semantic memory (score 16.05 ± 2.76) than men (score 6.59 ± 1.29 and 15.15 ± 2.92, respectively, P < 0.001 for both). In an adjusted multivariate model, fasting plasma glucose (fPG) and 2-h plasma glucose (2hPG) were significantly negatively associated with episodic memory (fPG: B -0.198, SE 0.068, β -0.209, P = 0.004; and 2hPG: B -0.061, SE 0.031, β -0.148, P = 0.048, respectively) in women but not in men. The association was not found in relation to semantic memory. CONCLUSIONS--We conclude that an increase in plasma glucose is associated with impairment in episodic memory in women. This could be explained by a negative effect on the hippocampus caused by raised plasma glucose levels. Diabetes 57:440-443, 2008 [ABSTRACT FROM AUTHOR]

The factorial structure of the Prospective and Retrospective Memory Questionnaire (PRMQ; Smith et al., 2000 ) was examined in a Swedish population based sample ( N= 540, age range; 35–90 years). Concurrent validity was assessed by relating PRMQ to global ratings of memory. Confirmatory factor analyses of the PRMQ items indicated a superior fit of a three-factor model, with prospective and retrospective memory as orthogonal factors and episodic memory as a common factor. Furthermore, the PRMQ scales correlated with the global ratings of memory, suggesting that each rating contributed with unique variance in predicting PRMQ scores. Given differences in levels of complaints as compared with prior research ( Crawford et al., 2003 ) norms for the Swedish version are provided. In conclusion, the present findings extend earlier work by providing additional support for the construct and concurrent validity of the PRMQ scales. [ABSTRACT FROM AUTHOR]

Gender differences have been reported regarding symptoms. prevalence and heritability of seasonal affective disorders (SAD). We focus on gender aspects in this study of self-reported seasonal changes in mood and behaviour in a general population. The Seasonal Pattern Assessment Questionnaire (SPAQ) was completed by 2620 adults (55.6% women) aged 15-85 years. enrolled in the Betula prospective random cohort study of Umeå. Sweden. October to February turned out to be suitable winter months. SAD was found in 2.2% and sub-syndromal SAD (S-SAD) in 5.7%. Women had about 1.5 times higher prevalences than men, and seasonality problems decreased with age in both genders. Preference for eating least was distributed with a peak in summer, whereas preference for eating most had a major peak in winter (winter eaters) and a minor peak in summer (summer eaters). Significantly more of winter eaters in women, and significantly more of summer caters in men, felt worst in winter. Seasonal change in weight was considered significantly as a problem by women but riot by men. Winter behaviour of sleeping most was considered significantly as a problem by men but not by women. Women reacted significantly to temperature-related changes (negatively to cold/short days and positively to hot/long days), whereas men reacted significantly to sunshine-related changes (negatively to cloudy days and positively to sunny days). Subtle gender differences may thus underlie the pathophysiology of seasonal problems. Studies of an eventual efficacy of treating SAD women with raised ambient temperature. and gender-specific comparisons with other therapies, would be of interest. [ABSTRACT FROM AUTHOR]

The article reports on research which was conducted to investigate whether the absence of natural teeth increased the risk of incident dementia. Researchers evaluated 2,075 subjects in an initial assessment and then 20 years later at a follow-up assessment. They found that dental status was unrelated to the risk of dementia.

Identification of novel candidate genes for schizophrenia (SZ) and bipolar disorder (BP), two psychiatric disorders with large epidemiological impacts, is a key research area in neurosciences and psychiatric genetics. Previous evidence from genome-wide studies suggests an important role for genes involved in synaptic plasticity in the risk for SZ and BP. We used a convergent genomics approach, combining different lines of biological evidence, to identify genes involved in the cAMP/PKA/CREB functional pathway that could be novel candidates for BP and SZ: CREB1, CREM, GRIN2C, NPY2R, NF1, PPP3CB and PRKAR1A. These 7 genes were analyzed in a HapMap based association study comprising 48 common SNPs in 486 SZ, 351 BP patients and 514 control individuals recruited from an isolated population in Northern Sweden. Genetic analysis showed significant allelic associations of SNPs in PRKAR1A with SZ and of PPP3CB and PRKAR1A with BP. Our results highlight the feasibility and the importance of convergent genomic data analysis for the identification of candidate genes and our data provide support for the role of common inherited variants in synaptic genes and their involvement in the etiology of BP and SZ. [ABSTRACT FROM AUTHOR]

Introduction: The objective was to examine whether subjective memory impairment (SMI) predicts all-cause dementia or Alzheimer's disease (AD) in a population-based study with long-term follow-up (median = 10 years)., Methods: A total of 2043 initially dementia-free participants (≥ 60 years) made three memory ratings ("compared with others", "compared with five years ago", and "complaints from family/friends") at baseline. During follow-up, 372 participants developed dementia (208 with AD)., Results: Cox regression revealed that subjective memory impairment ratings predicted all-cause dementia in models adjusting for age and sex (hazard ratio or HR from 2.04 to 3.94), with even higher values for AD (HR from 2.29 to 5.74). The result persisted in models including other covariates, including baseline episodic memory performance, and in analyses restricted to participants with long time to dementia diagnosis (≥ 5 years)., Discussion: The findings underscore the usefulness of subjective memory assessment in combination with other factors in identifying individuals at risk for developing dementia., (Copyright © 2015 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.)

Objectives: The aim of this study was to investigate whether leisure activity is associated with incident dementia in an older sample., Method: We examined a sample of 1,475 elderly (≥ 65 years) who were dementia free at baseline over a follow-up period of up to 15 years. In addition to analyses involving the total time period, separate analyses of three time periods were performed, 1-5, 6-10, and 11-15 years, following baseline measurement of leisure activity., Results: After controlling for a variety of potential confounders, analyses of data for the total time period revealed that higher levels of "Total activity" and "Social activity," but not "Mental activity," were associated with decreased risk of dementia. However, analyses of the separate time periods showed that this association was only significant in the first time period, 1-5 years after baseline., Discussion: The results from this study provide little support for the hypothesis that frequent engagement in leisure activities among elderly serve to protect against dementia diseases across a longer time frame. The finding of a relationship for the first time period, 1-5 years after baseline, could indicate short-term protective effects but could also reflect reverse causality., (© The Author 2013. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: This study examines the association between marital and parental status and their individual and combined effect on risk of dementia diseases in a population-based longitudinal study while controlling for a range of potential confounders, including social networks and exposure to stressful negative life events., Methods: A total of 1,609 participants without dementia, aged 65 years and over, were followed for an average period of 8.6 years (SD = 4.8). During follow-up, 354 participants were diagnosed with dementia. Cox regression was used to investigate the effect of marital and parental status on risk of dementia., Results: In univariate Cox regression models (adjusted for age as time scale), widowed (hazard ratio (HR) 1.42, 95% confidence interval (CI) = 1.13-1.78), and not having children (HR 1.54, 95% CI = 1.15-2.06) were significantly associated with incident dementia. In multivariate analyses that included simultaneously marital and parental status and covariates that were found to be significant in univariate models (p < 0.10), the HR was 1.30 (95% CI = 1.01-1.66) for widowed, and 1.51 (95% CI = 1.08-2.10) for those not having children. Finally, a group of four combined factors was constructed: married parents (reference), married without children, widowed parents, and widowed without children. The combined effect revealed a 1.3 times higher risk (95% CI = 1.03-1.76) of dementia in widow parents, and a 2.2 times higher risk (95% CI = 1.36-3.60) in widowed persons without children, in relation to married parents. No significant difference was observed for those being married and without children., Conclusions: Our findings suggest that marital- and parental status are important risk factors for developing dementia, with especially increased risk in those being both widowed and without children.

The rs1344706 single nucleotide polymorphism within intron 2 of the ZNF804A gene is strongly associated with schizophrenia and bipolar disorder. This variant has also been associated in some studies with a range of cognitive and neuroimaging phenotypes, but several studies have reported no effect on the same phenotypes in other samples. Here, we genotyped 670 healthy adult Norwegian subjects and 1753 healthy adult Swedish subjects for rs1344706, and tested for associations with cognitive phenotypes including general intellectual abilities, memory functions and cognitive inhibition. We also tested whether rs1344706 is associated with white matter microstructural properties using diffusion tensor imaging (DTI) data from 250 to 340 of the Norwegian and Swedish subjects, respectively. Whole-brain voxel-wise statistical modeling of the effect of the ZNF804A variant on two DTI indices, fractional anisotropy (FA) and radial diffusivity (RD), was performed using tract-based spatial statistics (TBSS), and commonly reported effect sizes were calculated within several large-scale white matter pathways based on neuroanatomical atlases. No significant associations were found between rs1344706 and the cognitive traits or white matter microstructure. We conclude that the rs1344706 SNP has no significant effect on these phenotypes in our two reasonably powered samples., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Background: The impact of stressful life events as a risk factor of dementia diseases is inconclusive. We sought to determine whether stressful negative life events are associated with incidental dementia in a population-based study with long-term follow-up. We also tested the hypothesis that the occurrence of positive life events could mitigate or overcome the possible adverse effects of negative life events on dementia conversion., Methods: The study involved 2,462 dementia-free participants aged 55 years and older. Information on life events was ascertained at baseline from a comprehensive Life Event Inventory, which included 56 questions about specific life events. For each life event, the emotional impact (both positive and negative) and emotional adjustment were asked for., Results: During follow-up, 423 participants developed dementia; of these, 240 developed Alzheimer's disease (AD). Cox regression analysis showed no association between the total number of negative life events and the incidence of dementia when adjusted solely for age and gender (hazard ratio = 0.97, 95% CI = 0.92-1.02), or with multiple adjustments for a range of covariates (hazard ratio = 0.96, 95% CI = 0.91-1.01). Similarly, neither emotional impact nor emotional adjustment to these life events was associated with incident dementia. A separate analysis of AD did not alter the results., Conclusions: The result of this population-based study finds no association between negative or positive life events and dementia. Accordingly, our results reject the hypothesis that stressful life events trigger the onset of dementia diseases.

In recent years, DISC1 has emerged as one of the most credible and best supported candidate genes for schizophrenia and related neuropsychiatric disorders. Furthermore, increasing evidence--both genetic and functional--indicates that many of its protein interaction partners are also involved in the development of these diseases. In this study, we applied a pooled sample 454 sequencing strategy, to explore the contribution of genetic variation in DISC1 and 10 of its interaction partners (ATF5, Grb2, FEZ1, LIS-1, PDE4B, NDE1, NDEL1, TRAF3IP1, YWHAE, and ZNF365) to schizophrenia susceptibility in an isolated northern Swedish population. Mutation burden analysis of the identified variants in a population of 486 SZ patients and 514 control individuals, revealed that non-synonymous rare variants with a MAF<0.01 were significantly more present in patients compared to controls (8.64% versus 4.7%, P = 0.018), providing further evidence for the involvement of DISC1 and some of its interaction partners in psychiatric disorders. This increased burden of rare missense variants was even more striking in a subgroup of early onset patients (12.9% versus 4.7%, P = 0.0004), highlighting the importance of studying subgroups of patients and identifying endophenotypes. Upon investigation of the potential functional effects associated with the identified missense variants, we found that ∼90% of these variants reside in intrinsically disordered protein regions. The observed increase in mutation burden in patients provides further support for the role of the DISC1 pathway in schizophrenia. Furthermore, this study presents the first evidence supporting the involvement of mutations within intrinsically disordered protein regions in the pathogenesis of psychiatric disorders. As many important biological functions depend directly on the disordered state, alteration of this disorder in key pathways may represent an intriguing new disease mechanism for schizophrenia and related neuropsychiatric diseases. Further research into this unexplored domain will be required to elucidate the role of the identified variants in schizophrenia etiology.

Background: The common cause account suggests that there is a third factor causing aging effects in both sensory and cognitive functioning, hypothesized to be the integrity of the central nervous system [Lindenberger and Baltes; Psychol Aging 1994;9:339-355]. Importantly, the common cause account was developed based on cross-sectional data, which are especially biased by cohort effects. However, cohort effects can be controlled for in narrow age cohort (NAC) designs and by longitudinal examination. Findings from the few longitudinal studies that have studied the relation between age-related changes in sensory and cognitive functions are complex and give only partial support to the common cause account., Objective: The present paper examines the common cause account within a longitudinal setting., Method: Our study is unique in the sense that it tests the common cause account within a longitudinal NAC design using data from the Betula project. The participants (n = 1,057) were in the age range of 45-90 years., Results: The findings indicate that the relationship between sensory and memory functioning in both a longitudinal age-heterogeneous and a longitudinal NAC design are much weaker than that detected by an age-heterogeneous cross-sectional design., Conclusion: The demonstrated weak age-associated sensory-cognitive link raises questions regarding the explanatory value of the common cause account and related theoretical accounts for accounting for age-related cognitive changes., (Copyright © 2010 S. Karger AG, Basel.)

Context: Neuregulin 1 (NRG1), a growth factor involved in neurodevelopment, myelination, neurotransmitter receptor expression, and synaptic plasticity, first joined the list of candidate genes for schizophrenia when a 7-marker haplotype at the 5' end of the gene (Hap(ICE)) was shown to be associated with the disorder in the Icelandic population. Since then, more genetic and functional evidence has emerged, which supports a role for NRG1 in the development of schizophrenia., Objective: To determine the contribution of NRG1 to susceptibility for schizophrenia in a northern Swedish isolated population., Design: Detailed linkage disequilibrium (LD)-based patient-control association study. This is the first study to type and analyze the 7 Hap(ICE) markers and a set of 32 HapMap tagging single-nucleotide polymorphisms (SNPs) that represents variants with a minor allele frequency of at least 1% and fully characterizes the LD structure of the 5' part of NRG1., Setting: Outpatient and inpatient hospitals., Participants: A total of 486 unrelated patients with schizophrenia and 514 unrelated control individuals recruited from a northern Swedish isolated population., Main Outcome Measures: Association between markers and disease., Results: Analysis of the Hap(ICE) markers showed the association of a 7-marker and 2-microsatellite haplotype, different from the haplotypes associated in the Icelandic population and overrepresented in northern Swedish control individuals. Subsequently, a more detailed analysis that included all 37 genotyped SNPs was performed by investigating haplotypic association, dependent and independent of LD block structure. We found significant association with 5 SNPs located in the second intron of NRG1 (.007

Through active reuptake of serotonin into presynaptic neurons, the serotonin transporter (5-HTT) plays an important role in regulating serotonin concentrations in the brain, and it is the site of binding for tricyclic antidepressants and selective serotonin reuptake inhibitors (SSRIs). Therefore it has been hypothesized that this transporter is involved in the etiology of bipolar (BP) disorder. Inconsistent association study results for the SLC6A4 gene encoding 5-HTT reported in literature emphasize the need for more systematic and detailed analyses of this candidate gene. We performed an extensive analysis of SLC6A4 on DNA of 254 BPI patients and 364 control individuals from a Northern Swedish isolated population. This analysis consisted of a HapMap LD-based association study including three widely investigated polymorphisms (5-HTTVNTR, 5-HTTLPR, and rs3813034), a copy-number variation (CNV) analysis and a mutation analysis of the complete coding sequence and the 3'-UTR of SLC6A4. No single marker showed statistically significant association with BPI, nor did any of the haplotypes. In the mutation analysis 13 novel variants were detected, including 2 amino acid substitutions M389V and I587L, but these are probably not implicated in risk for BP. No deletions or duplications were detected in the CNV analysis. We conclude that variation in the SLC6A4 gene or its regulatory regions does not contribute to the susceptibility for BP disorder in the Northern Swedish population.

The processing speed account suggests that general slowing of mental processing speed results in an overall decline, especially age-related decline, in other cognitive domains. Support for the speed account comes mainly from cross-sectional studies with participants that vary in age (age-heterogeneous samples). This study investigated how well variations in processing speed predict change of episodic recall in a longitudinal framework and examined with the Narrow Age Cohort (NAC) design. Data were obtained from Betula, a population-based longitudinal study. Both 5-year (n= 490; Time 3 - Time 4) and 10-year follow-up results (n= 608; Time 1 - Time 3) were used. In both samples, which were subjected to prospective dementia screening, we found considerably weaker associations in longitudinal data compared to cross-sectional, and also weaker associations in age-homogeneous than in age-heterogeneous samples. The results provide little support for the speed account.

Corticotropin-releasing factor-binding protein regulates the availability of free corticotropin-releasing factor and is a functional candidate gene for affective disorders. The aim of this study was to examine the association between polymorphisms in CRF-BP gene and bipolar disorder in an isolated Swedish population. One hundred and eighty-two patients with bipolar I disorder and 333 controls from Northern Sweden were included in the study. Five single nucleotide polymorphisms and a deletion polymorphism in the CRF-BP gene were genotyped. The haplotype block structure of the gene was considered and the expectation maximization algorithm was adopted to estimate the haplotype frequencies. As a result, there were no significant associations of the different polymorphisms in the CRF-BP gene with bipolar disorder. In conclusion, this study in an isolated Swedish population does not support a role for the CRF-BP gene in the vulnerability for bipolar disorder.

Background: Bipolar disorders are often not recognized. Several instruments were developed but none primarily focused on hypomania. The Hypomania Checklist (HCL) is aimed at the identification of bipolarity in outpatients. Using a German and Swedish sample, we investigated if the factor structure in nonclinical samples is similar to the one reported for outpatient samples. Furthermore, we tested if people who probably had a lifetime history of hypomania report more depression or other signs of impairment and if current depression is associated with lifetime hypomania., Method: In the German study, participants completed the HCL-32 as an online questionnaire that also included questions about lifetime and current depression (n = 695), whereas the Swedish data relied on the paper-and-pencil version of the HCL-32 completed by a random sample from a representative population sample (n = 408)., Results: The factor structure of the HCL-32 was fairly similar in both samples and to the ones presented by Angst et al (J Affect Disord 2005;88:217-33). People reporting "highs" (> or =4 days and experiencing negative consequences) not only endorsed more HCL-32 symptoms but also had higher rates of current and former depression and psychotherapy. Level of current depression was also associated with lifetime hypomanic symptoms. DISCUSSION AND LIMITATION: An "active-elated" and "risk-taking/irritable" factor of hypomania can be distinguished with the HCL-32 in clinical and nonclinical samples. Based on our results, the HCL-32 might even be useful as screening tool in nonclinical samples and not only in depressed outpatients. However, our data do not allow estimating sensitivity and specificity of the HCL-32 because structured clinical interviews were not included.

In two experiments, we examined the "Novelty-Encoding Hypothesis" proposed by Tulving and Kroll (1995), suggesting that the encoding of online information into long-term memory is influenced by its novelty and that novelty increases recognition performance. In Phase 1 (familiarization phase), subjects participated in a standard memory experiment in which different types of materials (verbs and nouns) were studied under different encoding conditions (enactment and non-enactment) and were tested by an expected recognition test. In Phase 2 (critical phase), subjects evaluated the materials (both familiar materials which were encoded earlier in Phase 1, and novel materials which were not presented earlier in Phase 1) in a frequency judgment task and were given an unexpected recognition test. The results of both experiments showed that novel items were recognized better than familiar items. This result held true for both hit rates - false alarms and hit rates. The novelty effect was observed for different subjects (Swedish and Japanese), different materials (verbs and nouns; high frequency and low frequency), and different types of encoding in Phase 1 (enactment and non-enactment). These findings provide support for the "Novelty-Encoding Hypothesis" stating that the effect is based on the encoding of target items at the time of the critical study (Phase 2). A comparison between the present experiments and the Tulving and Kroll (1995), Dobbins, Kroll, Yonelinas & Liu (1998) and Greene (1999) studies suggests that the novelty effect is more pronounced under incidental encoding than under intentional encoding.

Structural stability and change in semantic and episodic memory performance as well as interindividual differences in 5-year changes in these constructs are examined within a sample of older adults (age rangeT1 = 60-80; n = 361). Interindividual differences in change were limited but significant. Stability coefficients were higher for semantic memory (.95) than for episodic memory (.87). Changes in episodic and semantic memory performance were strongly associated (r =.68). Across time, variances and covariances increased, and a tendency toward dedifferentiation in terms of increasing correlations was found. Chronological age was related to both level and change, but gender and education were only related to level of memory performance. Collectively, these results depict relatively high degrees of structural stability and stability of interindividual differences in declarative memory in old age.

Background: The brain neurotransmitter serotonin is known to affect various aspects of human behavior, including personality traits. Serotonin receptor type 3 is a ligand-gated channel encoded by 2 different subunit genes, HTR3A and HTR3B. A polymorphism (C178T) in the 5' region of the HTR3A gene has recently been identified and suggested to be of functional importance., Objective: To elucidate the possible association between the C178T polymorphism in the HTR3A gene and personality traits in women., Design: Two independent samples of 35- to 45-year-old Swedish women were recruited using the population register. Sample 1 (n = 195) was assessed via the Karolinska Scales of Personality and the Temperament and Character Inventory; sample 2 (n = 175) was assessed using the latter only. Both samples were genotyped with respect to the C178T polymorphism in the HTR3A gene. The A1596G polymorphism in the same gene was also investigated., Results: A significant association between C178T genotype and the Temperament and Character Inventory factor harm avoidance was observed in sample 1 (corrected for multiple comparisons P =.04); this finding was subsequently replicated in sample 2 (P =.004) (pooled populations: P<.001). In the pooled sample, all harm avoidance subscales were found to be significantly associated with the C178T polymorphism: anticipatory worry (P =.001), fear of uncertainty (P<.001), shyness (P<.001), and fatigability and asthenia (P =.008). In addition, a significant association was found in sample 1 between the C178T polymorphism and the Karolinska Scales of Personality nonconformity factor (corrected P =.002), including the subscales of social desirability (P<.001), indirect aggression (P =.002), verbal aggression (P =.05), and irritability (P<.001). Participants homozygous for the less common T allele (<4%) differed from the remaining women by displaying lower ratings on harm avoidance and nonconformity., Conclusion: The C178T polymorphism in the HTR3A gene may affect the personality trait of harm avoidance in women.

Background: The relationship between cigarette smoking and cognitive function was examined in healthy Swedish adults who were participants in the Betula Prospective Cohort Study of Aging, Memory, and Health., Subjects: The data are from those individuals in the Betula study who were self-reported continuous smokers contrasted to those who reported never smoking cigarettes., Design: The dependent variables were cognitive tasks that varied with respect to difficulty and the demand they placed on processing resources., Results: Current smokers performed more poorly than never smokers on the more cognitively demanding tasks; namely, Block Design and free recall., Conclusions: The findings were interpreted in the light of the assumption that cigarette smoking may exert its greatest deleterious effect on those cognitive tasks that place the heaviest demands on processing resources.

The occurrence of cerebral white matter hyperintensities (WMHs), and their associations with blood pressure, episodic memory, and other cognitive tasks, were examined in a population-based sample of 123 individuals between 64 and 74 years old. Magnetic Resonance Imaging (MRI) detected subcortical and periventricular hyperintensities in 90% and 67% of the cases, respectively. Subcortical WMHs were related to elevated diastolic blood pressure measured ten years earlier, and periventricular WMHs were related to elevated diastolic blood pressure measured five and ten years earlier. Subcortical hyperintensities were weakly associated with impaired motor speed, but this association was not significant. Periventricular WMHs had a negative effect on episodic memory, although the relation was not linear. Collectively, the notion that white matter hyperintensities impair cognitive function got weak support in this Swedish sample.

Basic findings obtained on memory functions in normal aging are presented and discussed with respect to five separate but interacting memory systems. These systems are: episodic memory, semantic memory, short-term memory, perceptual representation system and procedural memory. All available evidence from cross-sectional research shows that there is a linear, decreasing memory performance as a function of age for episodic memory. Longitudinal studies suggest, however, that this age deficit may be an overestimation, by showing a relatively stable performance level up to middle age, followed by a sharp decline. Studies on semantic memory, short-term memory, perceptual representation system, and procedural memory show a relatively constant performance level across the adult life span, although some tasks used to assess short-term memory and procedural memory have revealed an age deficit. Disregarding the mixed results for these latter two memory systems, it can be concluded that episodic memory is unique in showing an age deficit. Episodic memory is also unique in the sense that it is the only memory system showing gender differences in performance throughout the adult life span with a significantly higher performance for women.

Objectives: To examine folic acid and vitamin B12 status in a group of 1000 persons sampled from the community of Umeå, Sweden, and aged 35, 40, 45, 50, 55, 60, 65, 70, 75 or 80 years. Reference data for folate and age-stratified reference data for vitamin B12 are presented, together with an examination of potential confounders., Measurements: All subjects participated in extensive health examinations and interviews, and laboratory blood testing was performed., Results: A series of exclusion criteria were applied, and data from 961 subjects were analysed. Vitamin B12 levels were found to decrease with increasing age, whereas folate levels remained constant across the age span studied. None of the vitamins was found to vary with sex, education, smoking or alcohol consumption, body mass index, prescription-free vitamin supplements, level of haemoglobin, or mean cell volume of erythrocytes. Further, none of these factors was associated with the age-related decrease of vitamin B12 level., Conclusions: The offered reference ranges should be used only in order to rule out deficiency. For B12 levels, the age of the subject should be considered such that, for elderly people in particular, values above the medians should be considered as indicative of normal vitamin status.