| 1. |
- Kauppi, Karolina, et al.
(författare)
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Effects of polygenic risk for Alzheimer's disease on rate of cognitive decline in normal aging
- 2020
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Ingår i: Translational Psychiatry. - : Nature Publishing Group. - 2158-3188. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Most people's cognitive abilities decline with age, with significant and partly genetically driven, individual differences in rate of change. Although APOE 4 and genetic scores for late-onset Alzheimer's disease (LOAD) have been related to cognitive decline during preclinical stages of dementia, there is limited knowledge concerning genetic factors implied in normal cognitive aging. In the present study, we examined three potential genetic predictors of age-related cognitive decline as follows: (1) the APOE 4 allele, (2) a polygenic score for general cognitive ability (PGS-cog), and (3) a polygenic risk score for late-onset AD (PRS-LOAD). We examined up to six time points of cognitive measurements in the longitudinal population-based Betula study, covering a 25-year follow-up period. Only participants that remained alive and non-demented until the most recent dementia screening (1-3 years after the last test occasion) were included (n=1087). Individual differences in rate of cognitive change (composite score) were predicted by the PRS-LOAD and APOE 4, but not by PGS-cog. To control for the possibility that the results reflected a preclinical state of Alzheimer's disease in some participants, we re-ran the analyses excluding cognitive data from the last test occasion to model cognitive change up-until a minimum of 6 years before potential onset of clinical Alzheimers. Strikingly, the association of PRS-LOAD, but not APOE 4, with cognitive change remained. The results indicate that PRS-LOAD predicts individual difference in rate of cognitive decline in normal aging, but it remains to be determined to what extent this reflects preclinical Alzheimer's disease brain pathophysiology and subsequent risk to develop the disease.
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| 2. |
- Nyberg, Lars, 1966-, et al.
(författare)
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Biological and environmental predictors of heterogeneity in neurocognitive ageing : Evidence from Betula and other longitudinal studies
- 2020
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Ingår i: Ageing Research Reviews. - : Elsevier. - 1568-1637 .- 1872-9649. ; 64
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Forskningsöversikt (refereegranskat)abstract
- Individual differences in cognitive performance increase with advancing age, reflecting marked cognitive changes in some individuals along with little or no change in others. Genetic and lifestyle factors are assumed to influence cognitive performance in aging by affecting the magnitude and extent of age-related brain changes (i.e., brain maintenance or atrophy), as well as the ability to recruit compensatory processes. The purpose of this review is to present findings from the Betula study and other longitudinal studies, with a focus on clarifying the role of key biological and environmental factors assumed to underlie individual differences in brain and cognitive aging. We discuss the vital importance of sampling, analytic methods, consideration of non-ignorable dropout, and related issues for valid conclusions on factors that influence healthy neurocognitive aging.
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| 3. |
- Börjesson, A, et al.
(författare)
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Linopirdine (DUP 996) : cholinergic treatment of older adults using successive and non-successive tests.
- 1999
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Ingår i: Neuropsychobiology. - 0302-282X .- 1423-0224. ; 40:2, s. 78-85
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of this study was to examine whether cholinergic treatment of age-associated memory impairment with Linopirdine (DUP 996), a derivate of phenylindoline, affects explicit memory, implicit memory, and primary memory. We also assessed cognitive decision making in a reaction time test. Explicit memory was assessed by face recognition, word recall and a word recognition test, being part of a successive test paradigm. Implicit memory was assessed by primed word fragment completion in the same successive test paradigm. Primary memory was studied by means of digit recall. Thirty-eight elderly subjects fulfilled the criteria for memory impairment. Four groups of subjects were given 10, 20 or 30 mg of DUP 996 or placebo during 4 weeks. A double-blind procedure was applied. No significant treatment effects for recognition memory and priming were obtained in the successive test paradigm. Analysis of dependence/independence between tests did not show any clear pattern of treatment effects. The other explicit memory tests and the reaction time test showed no effect with DUP 996. Because of the range of the different tests used here, the result and the general evidence in other investigations of the cholinergic depletion among aged people, the conclusion is that DUP 996 does not improve memory performance either in explicit, implicit or primary tests.
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| 4. |
- Eriksson Sörman, Daniel, et al.
(författare)
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Leisure Activity in Old Age and Risk of Dementia : a 15-Year Prospective Study
- 2014
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Ingår i: The journals of gerontology. Series B, Psychological sciences and social sciences. - : Oxford University Press. - 1079-5014 .- 1758-5368. ; 69:4, s. 493-501
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 5. |
- Eriksson Sörman, Daniel, et al.
(författare)
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Social relationships and risk of dementia : a population-based study
- 2015
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Ingår i: International psychogeriatrics. - : Cambridge University Press. - 1041-6102 .- 1741-203X. ; 27:8, s. 1391-1399
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 6. |
- Ronat, Lucas, et al.
(författare)
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Revised temperament and character inventory factors predict neuropsychiatric symptoms and aging-related cognitive decline across 25 years
- 2024
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Ingår i: Frontiers in Aging Neuroscience. - : Frontiers Media S.A.. - 1663-4365. ; 16
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Personality traits and neuropsychiatric symptoms such as neuroticism and depression share genetic overlap and have both been identified as risks factors for development of aging-related neurocognitive decline and Alzheimer’s disease (AD). This study aimed to examine revised personality factors derived from the Temperament and Character Inventory, previously shown to be associated with psychiatric disorders, as predictors of neuropsychiatric, cognitive, and brain trajectories of participants from a population-based aging study.Methods: Mixed-effect linear regression analyses were conducted on data for the full sample (Nmax = 1,286), and a healthy subsample not converting to AD-dementia during 25-year follow-up (Nmax = 1,145), complemented with Cox proportional regression models to determine risk factors for conversion to clinical AD.Results: Two personality factors, Closeness to Experience (CE: avoidance of new stimuli, high anxiety, pessimistic anticipation, low reward seeking) and Tendence to Liabilities (TL: inability to change, low autonomy, unaware of the value of their existence) were associated with higher levels of depressive symptoms, stress (CE), sleep disturbance (TL), as well as greater decline in memory, vocabulary and verbal fluency in the full sample. Higher CE was additionally associated with greater memory decline across 25 years in the healthy subsample, and faster right hippocampal volume reduction across 8 years in a neuroimaging subsample (N = 216). Most, but not all, personality-cognition associations persisted after controlling for diabetes, hypertension and cardiovascular disease. Concerning risks for conversion to AD, higher age, and APOE-ε4, but none of the personality measures, were significant predictors.Conclusion: The results indicate that personality traits associated with psychiatric symptoms predict accelerated age-related neurocognitive declines even in the absence of neurodegenerative disease. The attenuation of some personality effects on cognition after adjustment for health indicators suggests that those effects may be partly mediated by somatic health. Taken together, the results further emphasize the importance of personality traits in neurocognitive aging and underscore the need for an integrative (biopsychosocial) perspective of normal and pathological age-related cognitive decline.
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| 7. |
- Rönnlund, Michael, et al.
(författare)
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Perceived stress in adults aged 65 to 90 : Relations to facets of time perspective and COMT Val158Met polymorphism
- 2018
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Ingår i: Frontiers in Psychology. - : Frontiers Media S.A.. - 1664-1078. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- This study examined the relation between perceived stress and time perspective (views of past, present, future) in a population-based sample of older adults (65-90 years, N = 340). The Perceived Questionnaire (PSQ index) was used to measure stress and the Swedish version of the Zimbardo Time Perspective Inventory (S-ZTPI) was used to operationalize time perspective. Unlike the original inventory, S-ZTPI separates positive and negative aspects of a future time perspective and we hypothesized that the Future Negative (FN) scale would be important to account for variations in stress. Additionally, associations with Catechol-O-methyltransferase (COMT) Val(158)Met polymorphism were examined, motivated by prior associations of this single nucleotide polymorphism (SNP) with stress (or "anxiety") related personality traits. In line with the hypotheses, FN was the strongest predictor of PSQ index scores in multiple regression analyses. In a related vein, the dichotomization of the unitary Future scale increased the association between PSQ scores and a measure of deviations from a balanced time perspective, i.e., the difference between a proposed optimal and observed ZTPI profile. Finally, higher levels of stress as well as higher scores on FN were observed in COMT Val/Val carriers, at least among men. This suggests a shared dopaminergic genetic influence on these variables. Collectively, the results demonstrate that perceived stress is closely linked to time perspective and highlight the need to take negative aspects of a future temporal orientation into account to understand this relation.
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| 8. |
- Rönnlund, Michael, et al.
(författare)
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Self-reported memory failures : associations with future dementia in a population-based study with long-term follow-up
- 2015
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Ingår i: Journal of The American Geriatrics Society. - : Wiley-Blackwell. - 0002-8614 .- 1532-5415. ; 63:9, s. 1766-1773
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 9. |
- Rönnlund, Michael, et al.
(författare)
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Subjective memory impairment in older adults predicts future dementia independent of baseline memory performance : Evidence from the Betula prospective cohort study
- 2015
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Ingår i: Alzheimer's & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 11:11, s. 1385-1392
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Tidskriftsartikel (refereegranskat)abstract
- 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 followup (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.
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| 10. |
- Sundström, Anna, 1969-, et al.
(författare)
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Stressful life events are not associated with the development of dementia
- 2014
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Ingår i: International psychogeriatrics. - 1041-6102 .- 1741-203X. ; 26:1, s. 147-154
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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