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Nilsson, Lars-Göran
Alternative names
Publications (10 of 24) Show all publications
Athanasiu, L., Giddaluru, S., Fernandes, C., Christoforou, A., Reinvang, I., Lundervold, A. J., . . . Le Hellard, S. (2017). A genetic association study of CSMD1 and CSMD2 with cognitive function. Brain, behavior, and immunity, 61, 209-216
Open this publication in new window or tab >>A genetic association study of CSMD1 and CSMD2 with cognitive function
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2017 (English)In: Brain, behavior, and immunity, ISSN 0889-1591, E-ISSN 1090-2139, Vol. 61, p. 209-216Article in journal (Refereed) Published
Abstract [en]

The complement cascade plays a role in synaptic pruning and synaptic plasticity, which seem to be involved in cognitive functions and psychiatric disorders. Genetic variants in the closely related CSMD1 and CSMD2 genes, which are implicated in complement regulation, are associated with schizophrenia. Since patients with schizophrenia often show cognitive impairments, we tested whether variants in CSMD1 and CSMD2 are also associated with cognitive functions per se. We took a discovery-replication approach, using well-characterized Scandinavian cohorts. A total of 1637 SNPs in CSMD1 and 206 SNPs in CSMD2 were tested for association with cognitive functions in the NCNG sample (Norwegian Cognitive NeuroGenetics; n = 670). Replication testing of SNPs with p-value < 0.001 (7 in CSMD1 and 3 in CSMD2) was carried out in the TOP sample (Thematically Organized Psychosis; n =1025) and the BETULA sample (Betula Longitudinal Study on aging, memory and dementia; n = 1742). Finally, we conducted a meta-analysis of these SNPs using all three samples. The previously identified schizophrenia marker in CSMD1 (SNP rs10503253) was also included. The strongest association was observed between the CSMDI SNP rs2740931 and performance in immediate episodic memory (p-value = 5 Chi 10(-6), minor allele A, MAF 0.48-0.49, negative direction of effect). This association reached the study-wide significance level (p <= 1.2 Chi 10(-5)). SNP rs10503253 was not significantly associated with cognitive functions in our samples. In conclusion, we studied n = 3437 individuals and found evidence that a variant in CSMD1 is associated with cognitive function. Additional studies of larger samples with cognitive phenotypes will be needed to further clarify the role of CSMD1 in cognitive phenotypes in health and disease.

Keywords
Complement, Immunity, CSMD1, CSMD2, Schizophrenia, Cognition, Psychiatry, Memory, GWAS
National Category
Psychiatry Neurosciences
Identifiers
urn:nbn:se:umu:diva-133700 (URN)10.1016/j.bbi.2016.11.026 (DOI)000395365900023 ()27890662 (PubMedID)
Available from: 2017-04-18 Created: 2017-04-18 Last updated: 2018-11-12Bibliographically approved
Sörman Eriksson, D., Rönnlund, M., Sundström, A., Norberg, M. & Nilsson, L.-G. (2017). Social network size and cognitive functioning in middle-aged adults: cross-sectional and longitudinal associations. Journal of Adult Development, 24(2), 77-88
Open this publication in new window or tab >>Social network size and cognitive functioning in middle-aged adults: cross-sectional and longitudinal associations
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2017 (English)In: Journal of Adult Development, ISSN 1068-0667, E-ISSN 1573-3440, Vol. 24, no 2, p. 77-88Article in journal (Refereed) Published
Abstract [en]

The objective of the present study was to examine relations between social network size and three cognitive abilities (episodic memory, semantic memory, visuospatial ability) in middle-aged adults. We analyzed cross-sectional data on social network size and cognitive functioning that were available for 804 participants aged 40–60 years. In addition, we examined 5- and 10-year follow-up measurements of cognitive functioning that were available for 604 and 255 participants, respectively. Cross-sectional analyses revealed a positive association between social network size and each of the three cognitive abilities. Baseline network size was positively related to 5-year changes in semantic memory, and to 10-year changes in semantic as well as episodic memory, but was unrelated to changes in visuospatial performance. A minor portion of the sample (n = 131) had 10-year follow-up data on network size. Cross-lagged panel correlations revealed that baseline network size was associated with follow-up measurement in cognitive functioning (episodic memory, semantic memory), whereas baseline cognitive performance was unrelated to future network size. Together, the results demonstrate a small but positive relation between network size and declarative memory abilities, in line with models proposing a cognitive reserve built up by factors such as the increased cognitive stimulation associated with a more extensive social network.

Keywords
Cognition, Longitudinal, Cross-sectional, Social network, Cognitive reserve
National Category
Psychology Public Health, Global Health, Social Medicine and Epidemiology Sociology
Research subject
Psychology
Identifiers
urn:nbn:se:umu:diva-101832 (URN)10.1007/s10804-016-9248-3 (DOI)000399825300001 ()
Note

Originally published in manuscript form.

Available from: 2015-04-14 Created: 2015-04-14 Last updated: 2018-06-07Bibliographically approved
Stomby, A., Boraxbekk, C.-J., Lundquist, A., Nordin Adolfsson, A., Nilsson, L.-G., Adolfsson, R., . . . Olsson, T. (2016). Higher diurnal salivary cortisol levels are related to smaller prefrontal cortex surface area in elderly men and women. European Journal of Endocrinology, 175(2), 117-126
Open this publication in new window or tab >>Higher diurnal salivary cortisol levels are related to smaller prefrontal cortex surface area in elderly men and women
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2016 (English)In: European Journal of Endocrinology, ISSN 0804-4643, E-ISSN 1479-683X, Vol. 175, no 2, p. 117-126Article in journal (Refereed) Published
Abstract [en]

Objective: Elevated cortisol levels with aging have been associated with atrophy of the hippocampus and prefrontal cortex (PFC), as well as with impaired cognitive functions in men. However, coexisting diseases have confounded many studies examining these relationships. Studies in women are lacking. Our objective was to test whether salivary cortisol levels were related to morphology of the hippocampus and the PFC, and to cognitive performance. Design: A cross-sectional study including 200 elderly (55-80 years old) men and women. Method: We used magnetic resonance imaging, tests of episodic-, semantic-, and working memory, visuospatial ability, and cortisol levels in four saliva samples collected during 1 day. Results: Area under the curve (AUC) for cortisol levels was negatively related to cortical surface area of the left anterior cingulate gyrus (caudal P < 0.001; rostral P = 0.006), right lateral orbitofrontal cortex (P = 0.004), and right rostral middle frontal gyrus (P = 0.003). In women, there was also a negative relationship with cortical surface area in the left rostral middle frontal gyrus (P = 0.006). No relationship was found between cortisol levels and hippocampal volume. Conclusion: This study suggests that the structure of the medial PFC is related to cortisol levels in both elderly women and men.

National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:umu:diva-121117 (URN)10.1530/EJE-16-0352 (DOI)000380067200010 ()27190207 (PubMedID)
Available from: 2016-05-26 Created: 2016-05-26 Last updated: 2018-06-07Bibliographically approved
Davies, G., Armstrong, N., Bis, J. C., Bressler, J., Chouraki, V., Giddaluru, S., . . . Deary, I. J. (2015). Genetic contributions to variation in general cognitive function: a meta-analysis of genome-wide association studies in the CHARGE consortium (N=53 949). Molecular Psychiatry, 20(2), 183-192
Open this publication in new window or tab >>Genetic contributions to variation in general cognitive function: a meta-analysis of genome-wide association studies in the CHARGE consortium (N=53 949)
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2015 (English)In: Molecular Psychiatry, ISSN 1359-4184, E-ISSN 1476-5578, Vol. 20, no 2, p. 183-192Article in journal (Refereed) Published
Abstract [en]

General cognitive function is substantially heritable across the human life course from adolescence to old age. We investigated the genetic contribution to variation in this important, health-and well-being-related trait in middle-aged and older adults. We conducted a meta-analysis of genome-wide association studies of 31 cohorts (N = 53 949) in which the participants had undertaken multiple, diverse cognitive tests. A general cognitive function phenotype was tested for, and created in each cohort by principal component analysis. We report 13 genome-wide significant single-nucleotide polymorphism (SNP) associations in three genomic regions, 6q16.1, 14q12 and 19q13.32 (best SNP and closest gene, respectively: rs10457441, P = 3.93 x 10(-9), MIR2113; rs17522122, P = 2.55 x 10(-8), AKAP6; rs10119, P = 5.67 x 10(-9), APOE/TOMM40). We report one gene-based significant association with the HMGN1 gene located on chromosome 21 (P = 1x10(-6)). These genes have previously been associated with neuropsychiatric phenotypes. Meta-analysis results are consistent with a polygenic model of inheritance. To estimate SNP-based heritability, the genome-wide complex trait analysis procedure was applied to two large cohorts, the Atherosclerosis Risk in Communities Study (N = 6617) and the Health and Retirement Study (N = 5976). The proportion of phenotypic variation accounted for by all genotyped common SNPs was 29% (s.e. = 5%) and 28% (s.e. = 7%), respectively. Using polygenic prediction analysis, similar to 1.2% of the variance in general cognitive function was predicted in the Generation Scotland cohort (N = 5487; P = 1.5 x 10(-17)). In hypothesis-driven tests, there was significant association between general cognitive function and four genes previously associated with Alzheimer's disease: TOMM40, APOE, ABCG1 and MEF2C.

National Category
Neurology
Identifiers
urn:nbn:se:umu:diva-101412 (URN)10.1038/mp.2014.188 (DOI)000349986700007 ()25644384 (PubMedID)
Available from: 2015-04-30 Created: 2015-03-30 Last updated: 2018-06-07Bibliographically approved
Rönnlund, M., Sundström, A., Adolfsson, R. & Nilsson, L.-G. (2015). Self-reported memory failures: associations with future dementia in a population-based study with long-term follow-up. Journal of The American Geriatrics Society, 63(9), 1766-1773
Open this publication in new window or tab >>Self-reported memory failures: associations with future dementia in a population-based study with long-term follow-up
2015 (English)In: Journal of The American Geriatrics Society, ISSN 0002-8614, E-ISSN 1532-5415, Vol. 63, no 9, p. 1766-1773Article in journal (Refereed) Published
Abstract [en]

OBJECTIVES: To examine the association between self-reported memory failures and incident dementia in individuals aged 60 and older.

DESIGN: Longitudinal, community based.

SETTING: Betula Prospective Cohort Study, a population-based study in Umea, Sweden.

PARTICIPANTS: Individuals with a mean age of 71.5 +/- 8.8 (range 60-90) (N = 1,547).

MEASUREMENTS: Participants rated the frequency of everyday memory failures using the 16-item Prospective and Retrospective Memory Questionnaire (PRMQ) and underwent objective memory testing at baseline. Participant self-reports of complaints of poor memory by family and friends were evaluated. Dementia status was followed-up for 10 to 12 years.

RESULTS: Over the study period, 225 participants developed dementia (132 with Alzheimer's disease (AD)). In Cox proportional hazard regression models adjusted for demographic factors, PRMQ z-scores predicted incident dementia (hazard ratio (HR) = 1.21 for all-cause dementia; HR = 1.25 for AD, Ps < .01). The significant associations remained when depressive symptoms and objective memory performance were adjusted for, when low performers on objective memory (= 1 standard deviations below the age group mean) were excluded, and in analyses with delayed entry (survival time = 5 years). Similar patterns were observed for the prospective and retrospective subscales, although including how often participants self-reported that others complained about their poor memory eliminated the association between PRMQ scores and dementia and itself emerged as a significant predictor.

CONCLUSION: Self-reported memory failure predicted future dementia or AD independent of objective memory performance. Subjective reports of complaints by family and friends appear to be an even more-important indicator of preclinical impairments, and physicians should not ignore them, even in the absence of objective memory deficits.

Place, publisher, year, edition, pages
Wiley-Blackwell, 2015
Keywords
subjective memory, objective memory, dementia, Alzheimer's disease
National Category
Public Health, Global Health, Social Medicine and Epidemiology Geriatrics
Identifiers
urn:nbn:se:umu:diva-111769 (URN)10.1111/jgs.13611 (DOI)000363804800005 ()26280989 (PubMedID)2-s2.0-84942197349 (Scopus ID)
Available from: 2015-11-24 Created: 2015-11-23 Last updated: 2018-06-07Bibliographically approved
Eriksson Sörman, D., Rönnlund, M., Sundström, A., Adolfsson, R. & Nilsson, L.-G. (2015). Social relationships and risk of dementia: a population-based study. International psychogeriatrics, 27(8), 1391-1399
Open this publication in new window or tab >>Social relationships and risk of dementia: a population-based study
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2015 (English)In: International psychogeriatrics, ISSN 1041-6102, E-ISSN 1741-203X, Vol. 27, no 8, p. 1391-1399Article in journal (Refereed) Published
Abstract [en]

Background: The objective was to examine whether aspects of social relationships in old age are associated with all-cause dementia and Alzheimer's disease (AD).

Methods: We studied 1,715 older adults (≥ 65 years) who were dementia-free at baseline over a period of up to 16 years. Data on living status, contact/visit frequency, satisfaction with contact frequency, and having/not having a close friend were analyzed using Cox proportional hazards regressions with all-cause dementia or AD as the dependent variable. To control for reverse causality and to identify potential long-term effects, we additionally performed analyses with delayed entry.

Results: We identified 373 incident cases of dementia (207 with AD) during follow-up. The variable visiting/visits from friends was associated with reduced risk of all-cause dementia. Further, a higher value on the relationships index (sum of all variables) was associated with reduced risk of all-cause dementia and AD. However, in analyses with delayed entry, restricted to participants with a survival time of three years or more, none of the social relationship variables was associated with all-cause dementia or AD.

Conclusions: The results indicate that certain aspects of social relationships are associated with incident dementia or AD, but also that these associations may reflect reverse causality. Future studies aimed at identifying other factors of a person's social life that may have the potential to postpone dementia should consider the effects of reverse causality.

Place, publisher, year, edition, pages
Cambridge University Press, 2015
Keywords
dementia, Alzheimer's disease, longitudinal, social relationships, social network
National Category
Psychology
Identifiers
urn:nbn:se:umu:diva-101778 (URN)10.1017/S1041610215000319 (DOI)000361384500014 ()25779679 (PubMedID)
Available from: 2015-04-10 Created: 2015-04-10 Last updated: 2018-06-07Bibliographically approved
Rönnlund, M., Sundström, A., Adolfsson, R. & Nilsson, L.-G. (2015). Subjective memory impairment in older adults predicts future dementia independent of baseline memory performance: Evidence from the Betula prospective cohort study. Alzheimer's & Dementia, 11(11), 1385-1392
Open this publication in new window or tab >>Subjective memory impairment in older adults predicts future dementia independent of baseline memory performance: Evidence from the Betula prospective cohort study
2015 (English)In: Alzheimer's & Dementia, ISSN 1552-5260, E-ISSN 1552-5279, Vol. 11, no 11, p. 1385-1392Article in journal (Refereed) Published
Abstract [en]

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.

Keywords
Subjective memory impairment, Objective memory, Dementia, Alzheimer's disease
National Category
Neurosciences
Identifiers
urn:nbn:se:umu:diva-112734 (URN)10.1016/j.jalz.2014.11.006 (DOI)000365162900013 ()25667997 (PubMedID)
Available from: 2015-12-14 Created: 2015-12-14 Last updated: 2018-06-07Bibliographically approved
Nyberg, L., Andersson, M., Kauppi, K., Lundquist, A., Persson, J., Pudas, S. & Nilsson, L.-G. (2014). Age-related and genetic modulation of frontal cortex efficiency. Journal of cognitive neuroscience, 26(4), 746-754
Open this publication in new window or tab >>Age-related and genetic modulation of frontal cortex efficiency
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2014 (English)In: Journal of cognitive neuroscience, ISSN 0898-929X, E-ISSN 1530-8898, Vol. 26, no 4, p. 746-754Article in journal (Refereed) Published
Abstract [en]

The dorsolateral pFC (DLPFC) is a key region for working memory. It has been proposed that the DLPFC is dynamically recruited depending on task demands. By this view, high DLPFC recruitment for low-demanding tasks along with weak DLPFC upregulation at higher task demands reflects low efficiency. Here, the fMRI BOLD signal during working memory maintenance and manipulation was examined in relation to aging and catechol-O-methyltransferase (COMT) Val(158)Met status in a large representative sample (n = 287). The efficiency hypothesis predicts a weaker DLPFC response during manipulation, along with a stronger response during maintenance for older adults and COMT Val carriers compared with younger adults and COMT Met carriers. Consistent with the hypothesis, younger adults and met carriers showed maximal DLPFC BOLD response during manipulation, whereas older adults and val carriers displayed elevated DLPFC responses during the less demanding maintenance condition. The observed inverted relations support a link between dopamine and DLPFC efficiency.

National Category
Neurology Psychology
Identifiers
urn:nbn:se:umu:diva-89493 (URN)10.1162/jocn_a_00521 (DOI)000332021400005 ()
Available from: 2014-06-19 Created: 2014-06-03 Last updated: 2018-06-07Bibliographically approved
Nyström, M. B. .., Eriksson Sörman, D. & Nilsson, L.-G. (2014). Is Cognitive Functioning Important for Quality in Ageing?. In: Abstracts of the Psychonomic Society: . Paper presented at Psychonomic Society's 55th Annual Meeting (pp. 87-87).
Open this publication in new window or tab >>Is Cognitive Functioning Important for Quality in Ageing?
2014 (English)In: Abstracts of the Psychonomic Society, 2014, p. 87-87Conference paper, Poster (with or without abstract) (Refereed)
Abstract [en]

Well-being and happiness are two important aspects of quality in ageing. By using a large scale memory data base (the Betula study) the importance of cognitive status (episodic memory) for an individual’s subjective notion of well-being and happiness were investigated, both among middle- and old aged individuals. When a number of factors where controlled for (e.g., physical health, psycho-social aspects), results indicated no relationships between cognitive status and well-being or happiness, in any age group. However, data suggested that subjective experience of memory capacity seems to play an important role. Further, being married, having low levels of stress, and not having sleeping problems, also seem to be associated with both well-being and happiness. The result suggests that other factors, rather than cognitive status, plays a substantial roll in the quality of ageing. Future studies would benefit from using longitudinal data to be able to investigate these relationships over time.

Series
Abstracts of the Psychonomic Society ; 19
Keywords
Cognitive aging, happiness, well-being, memory, Betula
National Category
Psychology
Research subject
Psychology
Identifiers
urn:nbn:se:umu:diva-99307 (URN)
Conference
Psychonomic Society's 55th Annual Meeting
Available from: 2015-02-06 Created: 2015-02-06 Last updated: 2018-06-07Bibliographically approved
Fernandes, C. P., Westlye, L. T., Giddaluru, S., Christoforou, A., Kauppi, K., Adolfsson, R., . . . Espeseth, T. (2014). Lack of association of the rs1344706 ZNF804A variant with cognitive functions and DTI indices of white matter microstructure in two independent healthy populations. Psychiatry Research: Neuroimaging, 222(1-2), 60-66
Open this publication in new window or tab >>Lack of association of the rs1344706 ZNF804A variant with cognitive functions and DTI indices of white matter microstructure in two independent healthy populations
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2014 (English)In: Psychiatry Research: Neuroimaging, ISSN 0925-4927, E-ISSN 1872-7506, Vol. 222, no 1-2, p. 60-66Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
Elsevier, 2014
Keywords
fractional anisotropy, radial diffusivity, neuroimaging
National Category
Neurosciences Psychiatry
Identifiers
urn:nbn:se:umu:diva-87437 (URN)10.1016/j.pscychresns.2014.02.009 (DOI)000334739500008 ()24636489 (PubMedID)
Available from: 2014-04-01 Created: 2014-04-01 Last updated: 2018-06-08Bibliographically approved
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