| 1. |
- Ekström, Ingrid, et al.
(författare)
-
Smell Loss Predicts Mortality Risk Regardless of Dementia Conversion
- 2017
-
Ingår i: Journal of The American Geriatrics Society. - : Wiley. - 0002-8614 .- 1532-5415. ; 65:6, s. 1238-1243
-
Tidskriftsartikel (refereegranskat)abstract
- ObjectivesTo determine whether dementia could explain the association between poor olfactory performance and mortality risk within a decade-long follow-up period.DesignProspective cohort study.SettingBetula Study, Umeå, Sweden.ParticipantsA population-based sample of adult participants without dementia at baseline aged 40 to 90 (N = 1,774).MeasurementsOlfactory 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.ResultsWithin 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.ConclusionPoor 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.
|
|
| 2. |
- Larsson, Maria, et al.
(författare)
-
Loss of Olfactory Function Predicts Mortality Irrespective of Dementia Conversion : 10-year follow-up of an age-varied sample
- 2016
-
Ingår i: Chemical Senses. - : Oxford University Press (OUP). - 0379-864X .- 1464-3553. ; 41:9, s. e111-e288
-
Tidskriftsartikel (refereegranskat)abstract
- The objective of this study was to examine the association between performance in odor identification and future mortality in a community cohort of adults aged between 40 and 90 years. We assessed olfactory performance with a 13-item-version of the Scandinavian Odor Identification Test (SOIT). The results showed that during follow-up (mean=9.4 years, standard deviation=2.23), 411 of 1774 (23.2%) participants died. In a Cox model, the association between higher SOIT score and mortality was highly significant (hazard ratio [HR]=0.74, per point interval, 95% confidence interval [CI]=0.71–0.77, p<0.001). The effect was attenuated, but remained significant after controlling for age, sex, education, and health and cognitive variables that were also associated with an increased risk of mortality (HR=0.92, 95% CI=0.87–0.97, p=0.001). Controlling for dementia conversion prior to death did not attenuate the association between SOIT score and mortality (HR=0.92, 95% CI=0.87–0.97, p=0.001). Similar results were obtained for olfactory sensitivity as assessed by self-report. Overall, the present findings show that poor odor identification performance is associated with an increased likelihood of future mortality in middle-aged and older adults, after controlling for social, cognitive, and medical risk factors. Most importantly, controlling for the development of dementia did not attenuate the association between odor identification and mortality, suggesting that olfactory decline might mark deteriorating health also irrespective of dementia.
|
|
| 3. |
- Olofsson, Jonas K., et al.
(författare)
-
Long-term episodic memory decline is associated with olfactory deficits only in carriers of ApoE-є4
- 2016
-
Ingår i: Neuropsychologia. - : Elsevier BV. - 0028-3932 .- 1873-3514. ; 85, s. 1-9
-
Tidskriftsartikel (refereegranskat)abstract
- The ɛ4 allele of the Apolipoprotein E gene is a genetic risk factor for late-onset dementia of the Alzheimers' type (DAT), which is characterized by loss of both episodic memoryand olfactory functions. Little is known about the possible role of ɛ4 in the association between ongoing episodic memory decline and olfactory deficits in the general population, but such information is relevant in determining the relevance of olfaction as a marker of DAT risk. The present study was based on a large, population-based sample (n=1087, aged 45–90 years, of which 324 were ɛ4-carriers). Episodic memory change rates were established using data collected every 5 years for a 10–20 year interval leading up to an olfactory assessment using the Scandinavian Odor Identification Test at the last wave of data collection. Participants were classified according to whether or not their episodic memory ability declined more rapidly than the age-typical norm (by >1SD). Our main result is that only in ɛ4-carriers was episodic memory decline associated with odor identification impairment. In individuals without ɛ4, odor identification was unrelated to episodic memory decline status. Follow-up analyses indicated that this moderation by ɛ4 was due to the olfactory nature of the identification test, and that the effect was not caused by 63 individuals with dementia. Our results suggest that the ɛ4 determines the functional association between ongoing episodic memory decline and olfaction. These findings are consistent with the notion that ɛ4-carriers with DAT, compared to non-carriers, display a cortical atrophy pattern that is more focused on mediotemporal lobe regions supporting olfactory and episodic memory functions. Olfactory and memory assessments might provide complementary information on mediotemporal atrophy prior to clinical dementia onset, but the ɛ4 should be considered when using olfactory assessment as an early-stage indicator.
|
|
| 4. |
- Salami, Alireza, et al.
(författare)
-
Association of APOE ɛ4 and Plasma p-tau181 with Preclinical Alzheimer’s Disease and Longitudinal Change in Hippocampus Function
- 2022
-
Ingår i: Journal of Alzheimer's Disease. - : IOS Press. - 1387-2877 .- 1875-8908. ; 85:3, s. 1309-1320
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The Apolipoprotein E (APOE) ɛ4 allele has been linked to increased tau phosphorylation and tangle formation. APOE ɛ4 carriers with elevated tau might be at the higher risk for Alzheimer’s disease (AD) progression. Previous studies showed that tau pathology begins early in areas of the medial temporal lobe. Similarly, APOE ɛ4 carriers showed altered hippocampal functional integrity. However, it remains unknown whether the influence of elevated tau accumulation on hippocampal functional changes would be more pronounced for APOE ɛ4 carriers.Objective: We related ɛ4 carriage to levels of plasma phosphorylated tau (p-tau181) up to 15 years prior to AD onset. Furthermore, elevated p-tau181 was explored in relation to longitudinal changes in hippocampal function and connectivity.Methods: Plasma p-tau181 was analyzed in 142 clinically defined AD cases and 126 matched controls. The longitudinal analysis involved 87 non-demented individuals (from population-based study) with two waves of plasma samples and three waves of functional magnetic resonance imaging during rest and memory encoding.Results: Increased p-tau181 was observed for both ɛ4 carriers and non-carriers close to AD onset, but exclusively for ɛ4 carriers in the early preclinical groups (7- and 13-years pre-AD). In ɛ4 carriers, longitudinal p-tau181 increase was paralleled by elevated local hippocampal connectivity at rest and subsequent reduction of hippocampus encoding-related activity.Conclusion: Our findings support an association of APOE ɛ4 and p-tau181 with preclinical AD and hippocampus functioning.
|
|
| 5. |
- Stomby, Andreas, et al.
(författare)
-
Higher diurnal salivary cortisol levels are related to smaller prefrontal cortex surface area in elderly men and women
- 2016
-
Ingår i: European Journal of Endocrinology. - 0804-4643 .- 1479-683X. ; 175:2, s. 117-126
-
Tidskriftsartikel (refereegranskat)abstract
- 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.
|
|
| 6. |
- Boraxbekk, Carl-Johan, 1980-, et al.
(författare)
-
Free Recall Episodic Memory Performance Predicts Dementia Ten Years prior to Clinical Diagnosis : Findings from the Betula Longitudinal Study
- 2015
-
Ingår i: Dementia and Geriatric Cognitive Disorders Extra. - : S. Karger AG. - 1664-5464. ; 5:2, s. 191-202
-
Tidskriftsartikel (refereegranskat)abstract
- Background/Aims: Early dementia diagnosis is a considerable challenge. The present study examined the predictive value of cognitive performance for a future clinical diagnosis of late-onset Alzheimer's disease or vascular dementia in a random population sample. Methods: Cognitive performance was retrospectively compared between three groups of participants from the Betula longitudinal cohort. Group 1 developed dementia 11-22 years after baseline testing (n = 111) and group 2 after 1-10 years (n = 280); group 3 showed no deterioration towards dementia during the study period (n = 2,855). Multinomial logistic regression analysis was used to investigate the predictive value of tests reflecting episodic memory performance, semantic memory performance, visuospatial ability, and prospective memory performance. Results: Age-and education-corrected performance on two free recall episodic memory tests significantly predicted dementia 10 years prior to clinical diagnosis. Free recall performance also predicted dementia 11-22 years prior to diagnosis when controlling for education, but not when age was added to the model. Conclusion: The present results support the suggestion that two free recall-based tests of episodic memory function may be useful for detecting individuals at risk of developing dementia 10 years prior to clinical diagnosis.
|
|
| 7. |
- Ceulemans, Shana, et al.
(författare)
-
Evidence for the involvement of the glucocorticoid receptor gene in bipolar disorder in an isolated northern Swedish population
- 2011
-
Ingår i: Bipolar Disorders. - Malden, USA : John Wiley & Sons. - 1398-5647 .- 1399-5618. ; 13:7-8, s. 614-623
-
Tidskriftsartikel (refereegranskat)abstract
- 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.
|
|
| 8. |
- Moens, Lotte N, et al.
(författare)
-
Sequencing of DISC1 Pathway Genes Reveals Increased Burden of Rare Missense Variants in Schizophrenia Patients from a Northern Swedish Population
- 2011
-
Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 6:8, s. e23450-
-
Tidskriftsartikel (refereegranskat)abstract
- 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 similar to 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.
|
|
| 9. |
- Mousavi, Malahat, et al.
(författare)
-
Serum metabolomic biomarkers of dementia
- 2014
-
Ingår i: Dementia and Geriatric Cognitive Disorders Extra. - : S. Karger AG. - 1664-5464. ; 4:2, s. 252-62
-
Tidskriftsartikel (refereegranskat)abstract
- Aims: This study compared serum metabolites of demented patients (Alzheimer's disease and vascular dementia) and controls, and explored serum metabolite profiles of nondemented individuals 5 years preceding the diagnosis. Methods: Cognitively healthy participants were followed up for 5-20 years. Cognitive assessment, serum sampling, and diagnosis were completed every 5 years. Multivariate analyses were conducted on the metabolite profiles generated by gas chromatography/time-of-flight mass spectrometry. Results: A significant group separation was found between demented patients and controls, and between incident cases and controls. Metabolites that contributed in both analyses were 3,4-dihydroxybutanoic acid, docosapentaenoic acid, and uric acid. Conclusions: Serum metabolite profiles are altered in demented patients, and detectable up to 5 years preceding the diagnosis. Blood sampling can make an important contribution to the early prediction of conversion to dementia.
|
|
| 10. |
|
|
