| 1. |
- Codita, Alina, et al.
(författare)
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Impaired behavior of female tg-ArcSwe APP mice in the IntelliCage : A longitudinal study
- 2010
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Ingår i: Behavioural Brain Research. - : Elsevier BV. - 0166-4328 .- 1872-7549. ; 215:1, s. 83-94
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Tidskriftsartikel (refereegranskat)abstract
- Transgenic animals expressing mutant human amyloid precursor protein (APP) are used as models for Alzheimer disease (AD). Ideally, behavioral tests improve the predictive validity of studies on animals by mirroring the functional impact of AD-like neuropathology. Learning and memory studies in APP transgenic models have been difficult to replicate. Standardization of procedures, automatization or improved protocol design can improve reproducibility. Here the IntelliCage, an automated system, was used for behavioral testing of APP female transgenic mice with both the Arctic and Swedish mutations, the tg-ArcSwe model. Protocols covering exploration, operant learning, place learning and extinction of place preference as well as passive avoidance tests were used for longitudinal characterization of behavior. Differences in exploratory activity were significant at four months of age, when plaque-free tg-ArcSwe mice visited less frequently the IntelliCage corners and initially performed fewer visits with licks compared to non-tg animals, inside the new environment. Fourteen months old tg-ArcSwe mice required a longer time to re-habituate to the IntelliCages than non-tg mice. At both ages tg-ArcSwe mice perseverated in place preference extinction test. Fourteen months old tg-ArcSwe mice were impaired in hippocampus-dependent spatial passive avoidance learning. This deficit was found to inversely correlate to calbindin-D28k immunoreactivity in the polymorphic layer of the dentate gyrus. Reduced water intake and body weight were observed in 4 months old tg-ArcSwe animals. The body weight difference increased with age. Thus behavioral and metabolic changes in the tg-ArcSwe APP model were detected using the IntelliCage, a system which provides the opportunity for standardized automated longitudinal behavioral phenotyping.
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| 2. |
- Codita, Alina, et al.
(författare)
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Of mice and men : more neurobiology in dementia.
- 2006
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Ingår i: Curr Opin Psychiatry. - : Ovid Technologies (Wolters Kluwer Health). - 0951-7367. ; 19:6, s. 555-63
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 3. |
- Håkansson, Krister, 1952-, et al.
(författare)
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Association between mid-life marital status and cognitive function in later life : population based cohort study
- 2009
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Ingår i: The BMJ. - : BMJ. - 1756-1833 .- 0959-8138 .- 1468-5833. ; 339:July, s. Article number: b2462-
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Tidskriftsartikel (refereegranskat)abstract
- Objectives To evaluate whether mid-life marital status is related to cognitive function in later life. Design Prospective population based study with an average follow-up of 21 years. Setting Kuopio and Joensuu regions in eastern Finland. Participants Participants were derived from random, population based samples previously investigated in 1972, 1977, 1982, or 1987; 1449 individuals (73%), aged 65-79, underwent re-examination in 1998. Main outcome measures Alzheimer's disease and mild cognitive impairment. Results People cohabiting with a partner in mid-life (mean age 50.4) were less likely than all other categories (single, separated, or widowed) to show cognitive impairment later in life at ages 65-79. Those widowed or divorced in mid-life and still so at follow-up had three times the risk compared with married or cohabiting people. Those widowed both at mid-life and later life had an odds ratio of 7.67 (1.6 to 40.0) for Alzheimer's disease compared with married or cohabiting people. The highest increased risk for Alzheimer's disease was in carriers of the apolipoprotein E e4 allele who lost their partner before mid-life and were still widowed or divorced at follow-up. The progressive entering of several adjustment variables from mid-life did not alter these associations. Conclusions Living in a relationship with a partner might imply cognitive and social challenges that have a protective effect against cognitive impairment later in life, consistent with the brain reserve hypothesis. The specific increased risk for widowed and divorced people compared with single people indicates that other factors are needed to explain parts of the results. A sociogenetic disease model might explain the dramatic increase in risk of Alzheimer's disease for widowed apolipoprotein E e4 carriers.
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| 4. |
- Håkansson, Krister, 1952-, et al.
(författare)
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Feelings of hopelessness in midlife are associated with dementia risk in later life
- 2012
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Ingår i: 12th International Stockholm/Springfield Symposium on Advances in Alzheimer Therapy. ; , s. 165-165
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Background: Although an association between depressive feelings and dementia has been estab- lished previously, the nature of this relation remains unclear. Establishing causality has been com- plicated by the typical use of a short follow-up and aged participants already at baseline. The aim with this study was to investigate the association between feelings of hopelessness in midlife and cognitive impairment in later life.Methods: From a representative population in Eastern Finland, originally investigated between 1972-1987, a random sample of 2000 survivors was invited for re-examination in 1998, averagely 21 years later. The mean age of the 1449 persons who accepted the invitation was 50.4 (range 39-64) at baseline and 71.3 years (range 65-80) at follow-up. Baseline scores of hopelessness were related to cognitive status at follow-up, mainly through logistic regression. Adjustments were made for age, years of education, gender, APOE4 and a number of health and life style factors at baseline. In addition we analyzed differences in hopelessness scores between baseline and follow-up within the different outcome groups.Results: Participants with high levels of hopelessness at midlife had more than a doubled risk of cognitive impairment in later life as expressed by an odds ratio of 2.24 (1.4-3.6), even higher spe- cifically for Alzheimers disease. Persons with high levels of hopelessness at midlife and who in addition carried the apolipoprotein allele 4 (ApoE ε4) had a highly elevated risk of Alzheimers dis- ease. There were no significant differences in levels of hopelessness between baseline and follow-up within any of the outcome groups.Conclusions: The results confirm previous studies showing elevated scores of depressive feelings in persons diagnosed with dementia, compared to cognitively healthy persons. On the other hand, the results also suggest that the major portion of this difference could have existed already decades before the dementia diagnosis; Carrying feelings of hopelessness in midlife may have long-term implications for cognitive health in later life. Background: Although an association between depressive feelings and dementia has been estab- lished previously, the nature of this relation remains unclear. Establishing causality has been com- plicated by the typical use of a short follow-up and aged participants already at baseline. The aim with this study was to investigate the association between feelings of hopelessness in midlife and cognitive impairment in later life.Methods: From a representative population in Eastern Finland, originally investigated between 1972-1987, a random sample of 2000 survivors was invited for re-examination in 1998, averagely 21 years later. The mean age of the 1449 persons who accepted the invitation was 50.4 (range 39-64) at baseline and 71.3 years (range 65-80) at follow-up. Baseline scores of hopelessness were related to cognitive status at follow-up, mainly through logistic regression. Adjustments were made for age, years of education, gender, APOE4 and a number of health and life style factors at baseline. In addition we analyzed differences in hopelessness scores between baseline and follow-up within the different outcome groups.Results: Participants with high levels of hopelessness at midlife had more than a doubled risk of cognitive impairment in later life as expressed by an odds ratio of 2.24 (1.4-3.6), even higher spe- cifically for Alzheimers disease. Persons with high levels of hopelessness at midlife and who in addition carried the apolipoprotein allele 4 (ApoE ε4) had a highly elevated risk of Alzheimers dis- ease. There were no significant differences in levels of hopelessness between baseline and follow-up within any of the outcome groups.Conclusions: The results confirm previous studies showing elevated scores of depressive feelings in persons diagnosed with dementia, compared to cognitively healthy persons. On the other hand, the results also suggest that the major portion of this difference could have existed already decades before the dementia diagnosis; Carrying feelings of hopelessness in midlife may have long-term implications for cognitive health in later life.
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| 5. |
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| 6. |
- Ledreux, Aurelie, et al.
(författare)
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Differential Effects of Physical Exercise, Cognitive Training, and Mindfulness Practice on Serum BDNF Levels in Healthy Older Adults : A Randomized Controlled Intervention Study
- 2019
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Ingår i: Journal of Alzheimer's Disease. - : IOS Press. - 1387-2877 .- 1875-8908. ; 71:4, s. 1245-1261
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Tidskriftsartikel (refereegranskat)abstract
- Previous studies have indicated that an active lifestyle is associated with better brain health and a longer life, compared to a more sedentary lifestyle. These studies, both on human and animal subjects, have typically focused on a single activity, usually physical exercise, but other activities have received an increasing interest. One proposed mechanism is that physical exercise increases levels of brain-derived neurotrophic factor (BDNF) in the brain. For the first time, the long-term effects on serum BDNF levels were compared in persons who engaged in either physical exercise training, cognitive training, or mindfulness practice during 5 weeks, and compared with an active control group. Two cohorts of healthy older individuals, one from the Boston area in the US and one from the Vaxjo area in Sweden, participated. A total of 146 participants were randomly assigned to one of the four groups. All interventions were structurally similar, using interactive, computer-based software that directed participants to carry out specified activities for 35 minutes/day, 5 days per week for 5 weeks. Blood samples were obtained at baseline and soon after the completion of the 5-week long intervention program, and serum BDNF levels were measured using a commercially available ELISA. Only the group that underwent cognitive training increased their serum BDNF levels after 5 weeks of training (F-1,F-74 = 4.22, p = 0.044, partial eta(2) = 0.054), corresponding to an average 10% increase. These results strongly suggest that cognitive training can exert beneficial effects on brain health in an older adult population.
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| 7. |
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| 8. |
- Zhu, Shun-Wei, et al.
(författare)
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Influence of environmental manipulation on exploratory behaviour in male BDNF knockout mice
- 2009
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Ingår i: Behavioural Brain Research. - : Elsevier BV. - 0166-4328 .- 1872-7549. ; 197:2, s. 339-346
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Tidskriftsartikel (refereegranskat)abstract
- It is widely accepted that brain derived neurotrophic factor (BDNF) plays a crucial role in mediating changes in learning and memory performance induced by environmental conditions. In order to ascertain whether BDNF modulates environmentally induced changes in exploratory behaviour, we examined mice carrying a deletion in one copy of the BDNF gene. Young heterozygous male BDNF knockout mice (BDNF+/−) and their wild-type (WT) controls were exposed to the enriched environment condition (EC) or the standard condition (SC) for 8 weeks. Exploratory behaviour was assessed in the open-field (OF) and hole-board (HB) test. Brains from EC and SC reared animals were processed for Golgi-Cox staining and the dendritic spine density in the dentate gyrus (DG) and CA1 hippocampal regions were examined. We found behavioural differences both due to the genetic modification and the environmental manipulation, with the BDNF+/− mice being more active in the OF whereas the EC mice had increased exploratory behaviour in the HB test. Environmental enrichment also led to an increase in dendritic spines in the hippocampal CA1 region and DG of the wild-type mice. This effect was also found in the enriched BDNF+/− mice, but was less pronounced. Our findings support the critical role of BDNF in behavioural and neural plasticity associated with environmental enrichment and suggest that besides maze learning performance, BDNF dependent mechanisms are also involved in other aspects of behaviour. Here we provide additional evidence that exploratory activity is influenced by BDNF.
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