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  • 1.
    Behforuzi, Hura
    et al.
    Harvard Med Sch, USA.
    Feng, Nicole C.
    Harvard Med Sch, USA.
    Billig, Adam R.
    Harvard Med Sch, USA.
    Ryan, Eliza
    Harvard Med Sch, USA.
    Tusch, Erich S.
    Harvard Med Sch, USA.
    Holcomb, Phillip J.
    San Diego State Univ, USA.
    Mohammed, Abdul K. H.
    Linnéuniversitetet, Fakulteten för Hälso- och livsvetenskap (FHL), Institutionen för psykologi (PSY). Karolinska Institutet, Sweden.
    Daffner, Kirk R.
    Harvard Med Sch, USA.
    Markers of Novelty Processing in Older Adults Are Stable and Reliable2019Ingår i: Frontiers in Aging Neuroscience, ISSN 1663-4365, E-ISSN 1663-4365, Vol. 11, s. 1-15, artikel-id 165Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Exploratory behavior and responsiveness to novelty play an important role in maintaining cognitive function in older adults. Inferences about age- or disease-related differences in neural and behavioral responses to novelty are most often based on results from single experimental testing sessions. There has been very limited research on whether such findings represent stable characteristics of populations studied, which is essential if investigators are to determine the result of interventions aimed at promoting exploratory behaviors or draw appropriate conclusions about differences in the processing of novelty across diverse clinical groups. The goal of the current study was to investigate the short-term test-retest reliability of event-related potential (ERP) and behavioral responses to novel stimuli in cognitively normal older adults. ERPs and viewing durations were recorded in 70 healthy older adults participating in a subject-controlled visual novelty oddball task during two sessions occurring 7 weeks apart. Mean midline P3 amplitude and latency, mean midline amplitude during successive 50 ms intervals, temporospatial factors derived from principal component analysis (PCA), and viewing duration in response to novel stimuli were measured during each session. Analysis of variance (ANOVA) revealed no reliable differences in the value of any measurements between Time 1 and 2. Intraclass correlation coefficients (ICCs) between Time 1 and 2 were excellent for mean P3 amplitude (ICC = 0.86), the two temporospatial factors consistent with the P3 components (ICC of 0.88 and 0.76) and viewing duration of novel stimuli (ICC = 0.81). Reliability was only fair for P3 peak latency (ICC = 0.56). Successive 50 ms mean amplitude measures from 100 to 1,000 ms yielded fair to excellent reliabilities, and all but one of the 12 temporospatial factors identified demonstrated ICCs in the good to excellent range. We conclude that older adults demonstrate substantial stability in ERP and behavioral responses to novel visual stimuli over a 7-week period. These results suggest that older adults may have a characteristic way of processing novelty that appears resistant to transient changes in their environment or internal states, which can be indexed during a single testing session. The establishment of reliable measures of novelty processing will allow investigators to determine whether proposed interventions have an impact on this important aspect of behavior.

  • 2. Bjartmar, Lisa
    et al.
    Alkhori, Liza
    Ruud, Johan
    Mohammed, Abdul K. H.
    Linnéuniversitetet, Fakultetsnämnden för hälsa, socialt arbete och beteendevetenskap, Institutionen för pedagogik, psykologi och idrottsvetenskap, PPI. Karolinska Institutet.
    Marcusson, Jan
    Hallbeck, Martin
    Long-term treatment with antidepressants, but not environmental stimulation, induces expression of NP2 mRNA in hippocampus and medial habenula.2010Ingår i: Brain Research, ISSN 0006-8993, E-ISSN 1872-6240, Vol. 1328, s. 25-33Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    In experimental settings, antidepressant treatment as well as a stimulating environment has a positive influence on cognition and hippocampal plasticity. One putative mediator of this process is Neuronal Pentraxin 2 (NP2, Narp), known to mediate clustering of glutamatergic AMPA receptors at synapses, and demonstrated to play a role in activity-dependent synaptogenesis and synaptic plasticity. This study demonstrates that NP2 mRNA is robustly expressed in all hippocampal subregions and the medial habenula (MHb), both regions implicated in cognitive functions. Furthermore, NP2 mRNA expression is upregulated in the hippocampal subregions as well as in the MHb after long-term treatment with different antidepressant drugs regardless of monoaminergic profile, suggesting NP2 as a common mode of action of different antidepressant drugs. This effect occurs at the time frame where clinical response is normally achieved. In contrast, neither environmental enrichment nor deprivation has any influence on long-term NP2 mRNA expression. These findings support an involvement of NP2 in the pathway of antidepressant-induced plasticity, but not EE-induced plasticity; that NP2 might constitute a common link for the action of different types of antidepressant drugs and that the MHb could be a putative region for further studies of NP2.

  • 3. Codita, Alina
    et al.
    Gumucio, Astrid
    Lannfelt, Lars
    Gellerfors, Pär
    Winblad, Bengt
    Mohammed, Abdul K. H.
    Linnéuniversitetet, Fakultetsnämnden för hälsa, socialt arbete och beteendevetenskap, Institutionen för pedagogik, psykologi och idrottsvetenskap, PPI. Karolinska institutet.
    Nilsson, Lars N G
    Impaired behavior of female tg-ArcSwe APP mice in the IntelliCage: A longitudinal study.2010Ingår i: Behavioural Brain Research, ISSN 0166-4328, E-ISSN 1872-7549, Vol. 215, nr 1, s. 83-94Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    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.

  • 4.
    Codita, Alina
    et al.
    Karolinska Institutet.
    Mohammed, Abdul K. H.
    Linnéuniversitetet, Fakultetsnämnden för hälsa, socialt arbete och beteendevetenskap, Institutionen för pedagogik, psykologi och idrottsvetenskap, PPI. Karolinska Institutet.
    Willuweit, Antje
    Evotec Neurosci GmbH, Germany.
    Reichelt, Anja
    Evotec Neurosci GmbH, Germany.
    Alleva, Enrico
    Istituto Superiore di Sanità, Italy.
    Branchi, Igor
    Istituto Superiore di Sanità, Italy.
    Cirulli, Francesca
    Istituto Superiore di Sanità, Italy.
    Colacicco, Giovanni
    University of Zürich, Switzerland.
    Voikar, Vootele
    University of Zürich, Switzerland.
    Wolfer, David P
    University of Zürich, Switzerland.
    Buschmann, Frank J U
    FBI Science GmbH, Germany .
    Lipp, Hans-Peter
    University of Zürich, Switzerland ; NewBehavior AG, Switzerland.
    Vannoni, Elisabetta
    University of Zürich, Switzerland ; NewBehavior AG, Switzerland.
    Krackow, Sven
    University of Zürich, Switzerland ; NewBehavior AG, Switzerland ; Humboldt University, Germany.
    Effects of spatial and cognitive enrichment on activity pattern and learning performance in three strains of mice in the IntelliMaze.2012Ingår i: Behavior Genetics, ISSN 0001-8244, E-ISSN 1573-3297, Vol. 42, nr 3, s. 449-460Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The IntelliMaze allows automated behavioral analysis of group housed laboratory mice while individually assigned protocols can be applied concomitantly for different operant conditioning components. Here we evaluate the effect of additional component availability (enrichment) on behavioral and cognitive performance of mice in the IntelliCage, by focusing on aspects that had previously been found to consistently differ between three strains, in four European laboratories. Enrichment decreased the activity level in the IntelliCages and enhanced spatial learning performance. However, it did not alter strain differences, except for activity during the initial experimental phase. Our results from non-enriched IntelliCages proved consistent between laboratories, but overall laboratory-consistency for data collected using different IntelliCage set-ups, did not hold for activity levels during the initial adaptation phase. Our results suggest that the multiple conditioning in spatially and cognitively enriched environments are feasible without affecting external validity for a specific task, provided animals have adapted to such an IntelliMaze.

  • 5. Codita, Alina
    et al.
    Winblad, Bengt
    Mohammed, Abdul K. H.
    Växjö universitet, Fakulteten för humaniora och samhällsvetenskap, Institutionen för samhällsvetenskap.
    Of mice and men: more neurobiology in dementia.2006Ingår i: Curr Opin Psychiatry, ISSN 0951-7367, Vol. 19, nr 6, s. 555-63Artikel i tidskrift (Övrigt vetenskapligt)
  • 6. Darmopil, Sanja
    et al.
    Petanjek, Zdravko
    Mohammed, Abdul K. H.
    Växjö universitet, Fakulteten för humaniora och samhällsvetenskap, Institutionen för samhällsvetenskap.
    Bogdanovic, Nenad
    Environmental enrichment alters dentate granule cell morphology in oldest-old rat2009Ingår i: Journal of Cellular and Molecular Medicine (Print), ISSN 1582-1838, E-ISSN 1582-4934, Vol. 13, nr 8b, s. 1845-1856Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The hippocampus of aged rats shows marked age-related morphological changes that could cause memory deficits. Experimental evidence has established that environmental enrichment attenuates memory deficits in aged rats. We therefore studied whether environmental enrichment produces morphological changes on the dentate granule cells of aged rats. Fifteen male Sprague-Dawley rats, 24 months of age, were randomly distributed in two groups that were housed under standard (n= 7) or enriched (n= 8) environmental conditions for 26 days. Quantitative data of dendritic morphology from dentate gyrus granule cells were obtained on Golgi–Cox stained sections. Environmental enrichment significantly increased the complexity and size of dendritic tree (total number of segments increased by 61% and length by 116%), and spine density (88% increase). There were large interindividual differences within the enriched group, indicating differential individual responses to environmental stimulation. Previous studies in young animals have shown changes produced by environmental enrichment in the morphology of dentate gyrus granule cells. The results of the present study show that environmental enrichment can also produce changes in dentate granule cell morphology in the senescent brain. In conclusion, the hippocampus retains its neuroplastic capacity during aging, and enriched environmental housing conditions can attenuate age-related dendritic regression and synaptic loss, thus preserving memory functions.

  • 7.
    Feng, Nicole C.
    et al.
    Harvard Medical School, USA.
    Ryan, Eliza
    Harvard Medical School, USA.
    Tewele, Mhretab Kidane
    Linnéuniversitetet, Fakulteten för teknik (FTK), Institutionen för datavetenskap och medieteknik (DM).
    Tusch, Erich S.
    Harvard Medical School, USA.
    McFeeley, Brittany M.
    Harvard Medical School, USA.
    Carlsson, Roger
    Linnéuniversitetet, Fakulteten för Hälso- och livsvetenskap (FHL), Institutionen för psykologi (PSY).
    Mohammed, Abdul K. H.
    Linnéuniversitetet, Fakulteten för Hälso- och livsvetenskap (FHL), Institutionen för psykologi (PSY). Karolinska Institutet, Sweden.
    Håkansson, Krister
    Linnéuniversitetet, Fakulteten för Hälso- och livsvetenskap (FHL), Institutionen för psykologi (PSY).
    Daffner, Kirk R.
    Harvard Medical School, USA.
    Feasibility of an at-home, web-based, interactive exercise program for older adults2019Ingår i: Alzheimer’s & Dementia: Translational Research & Clinical Interventions (TRCI), ISSN 2352-8737, Vol. 5, nr 1, s. 825-833Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Introduction: Increased physical exercise is linked to enhanced brain health and reduced dementia risk. Exercise intervention studies usually are conducted at facilities in groups under trainer supervision. To improve scalability, accessibility, and engagement, programs may need to be structured such that individuals can execute and adjust routines in their own homes.

    Methods: One hundred eighty-three healthy older adults from two sites (the United States and Sweden) were screened. One hundred fifty-six subjects (mean age 73.2), randomly assigned to one of four interventions (PACE-Yourself physical exercise program, mindfulness meditation, or Cogmed® adaptive or nonadaptive computerized working memory training) began the study. All interventions were structurally similar: occurring in subjects' homes using interactive, web-based software, over five weeks, ∼175 minutes/week. In the PACE-Yourself program, video segments presented aerobic exercises at different pace and intensity (P&I). The program paused frequently, allowing subjects to indicate whether P&I was "too easy," "too hard," or "somewhat hard." P&I of the subsequent exercise set was adjusted, allowing subjects to exercise at a perceived exertion level of "somewhat hard." Program completion was defined as finishing ≥60% of sessions.

    Results: A high percentage of participants in all groups completed the program, although the number (86%) was slightly lower in the PACE-Yourself group than the other three. Excluding dropouts, the PACE-Yourself group had a lower adherence rate of 93%, compared with the other three (∼98%). Over the five weeks, PACE-Yourself participants increased exercising at the highest intensity level, consistent with augmented aerobic activity over time. The number of exercise sessions completed predicted the postintervention versus preintervention increase in self-reported level of physical activity.

    Discussion: This study supports the feasibility of a home-based, subject-controlled, exercise program in which P&I is regulated via real-time participant feedback, which may promote self-efficacy. Further study is needed to determine if similar results are found over longer periods and in more diverse populations.

  • 8.
    Hamlett, Eric D.
    et al.
    Medical University of Southern Carolina, USA ; University of Denver, USA.
    Goetzl, Edward J.
    Jewish Home of San Francisco, USA ; University of California, USA.
    Ledreux, Aurélie
    Medical University of Southern Carolina, USA ; University of Denver, USA.
    Vasilevko, Vitaly
    University of California, USA.
    Boger, Heather A.
    Medical University of Southern Carolina, USA.
    LaRosa, Angela
    Medical University of Southern Carolina, USA.
    Clark, David
    Medical University of Southern Carolina, USA.
    Carroll, Steven L.
    Medical University of Southern Carolina, USA.
    Carmona-Iragui, María
    Biomedical Research Institute Sant Pau, Spain ; Down Medical Centre, Spain.
    Fortea, Juan
    Biomedical Research Institute Sant Pau, Spain ; Down Medical Centre, Spain.
    Mufson, Elliott J.
    Barrow Neurological Institute, USA.
    Sabbagh, Marwan
    Barrow Neurological Institute, USA.
    Mohammed, Abdul K. H.
    Linnéuniversitetet, Fakulteten för Hälso- och livsvetenskap (FHL), Institutionen för psykologi (PSY). Karolinska Institutet.
    Hartley, Dean
    Alzheimer's Association, USA.
    Doran, Eric
    University of California, USA.
    Lott, Ira T.
    University of California, USA.
    Granholm, Ann-Charlotte
    Medical University of Southern Carolina, USA.
    Neuronal exosomes reveal Alzheimer's disease biomarkers in Down syndrome2017Ingår i: Alzheimer's & Dementia, ISSN 1552-5260, E-ISSN 1552-5279, Vol. 13, nr 5, s. 541-549Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    INTRODUCTION: Individuals with Down syndrome (DS) exhibit Alzheimer's disease (AD) neuropathology and dementia early in life. Blood biomarkers of AD neuropathology would be valuable, as non-AD intellectual disabilities of DS and AD dementia overlap clinically. We hypothesized that elevations of amyloid-β (Aβ) peptides and phosphorylated-tau in neuronal exosomes may document preclinical AD.

    METHODS: AD neuropathogenic proteins Aβ1-42, P-T181-tau, and P-S396-tau were quantified by enzyme-linked immunosorbent assays in extracts of neuronal exosomes purified from blood of individuals with DS and age-matched controls.

    RESULTS: Neuronal exosome levels of Aβ1-42, P-T181-tau, and P-S396-tau were significantly elevated in individuals with DS compared with age-matched controls at all ages beginning in childhood. No significant gender differences were observed.

    DISCUSSION: These early increases in Aβ1-42, P-T181-tau, and P-S396-tau in individuals with DS may provide a basis for early intervention as targeted treatments become available.

  • 9.
    Håkansson, Krister
    et al.
    Karolinska Institutet.
    Helkala, Eeva-Liisa
    University of Kuopio,, Kuopio, Finland.
    Soininen, Hilkka
    University of Kuopio,, Kuopio, Finland.
    Nissinen, Aulikki
    National Institute for Health and Welfare, Helsinki, Finland.
    Mohammed, Abdul K. H.
    Linnéuniversitetet, Fakultetsnämnden för hälsa, socialt arbete och beteendevetenskap, Institutionen för pedagogik, psykologi och idrottsvetenskap, PPI. Karolinska institutet.
    Winblad, Bengt
    Karolinska Institutet.
    Kivipelto, Miia
    Karolinska Institutet.
    Perceived marital problems in midlife are associated with cognitive health in later life2010Ingår i: Alzheimer's & Dementia, ISSN 1552-5260, E-ISSN 1552-5279, Vol. 7, nr 4, Supplement, s. 595-595Artikel i tidskrift (Övrigt vetenskapligt)
  • 10.
    Håkansson, Krister
    et al.
    Linnéuniversitetet, Fakultetsnämnden för hälsa, socialt arbete och beteendevetenskap, Institutionen för pedagogik, psykologi och idrottsvetenskap, PPI.
    Helkala, E.L.
    University of Eastern Finland, Kuopio.
    Soininen, H.
    University of Eastern Finland, Kuopio.
    Nissinen, A.
    National Institute for Health and Welfare, Helsinki.
    Winblad, B.
    Karolinska Institutet.
    Mohammed, Abdul K. H.
    Linnéuniversitetet, Fakultetsnämnden för hälsa, socialt arbete och beteendevetenskap, Institutionen för pedagogik, psykologi och idrottsvetenskap, PPI.
    Kivipelto, M.
    Karolinska Institutet.
    Depressive signs in midlife: A risk factor for cognitive impairment in later life?2010Ingår i: International Conference on Alzheimer's Disease (ICAD) 2010, Chicago, USA: Alzheimer's Association , 2010Konferensbidrag (Refereegranskat)
    Abstract [en]

    Background: Although depression has been associated with dementia, the nature of this relation is still unclear. Establishing causality from previous studies has been complicated by the typical use of a short follow-up and participants aged over 70 already at baseline. The main purpose of this study was to evaluate if depressive signs already in midlife are related to cognitive impairment in later life. Methods: Participants were derived from random, population-based samples previously investigated in 1972, 1977, 1982, or 1987. Their mean age at baseline was 50.4 years (SD 6.0). After an average follow-up of 21 years, 1449 individuals (73%) aged 65 to 79 years were re-examined in 1998. At the re-examination some form of cognitive impairment was diagnosed in 139 of the participants: 82 with mild cognitive impairment and 57 with dementia (48 of these with Alzheimer’s disease). Signs of depression were estimated through responses to three questions concerning the perception of a hopeless future, impossible life goals and loneliness. The relation between depressive signs in midlife and cognitive impairment in later life was analyzed with logistic regression with adjustments for age, gender, apolipoprotein e4 status and a number of midlife health and lifestyle indicators, including blood pressure, cholesterol and marital status. Results: Depressive signs in midlife, as measured in this study, were significantly related to general cognitive impairment in later life, but also separately to both mild cognitive impairment and Alzheimer’s disease. When dichotomized into high versus low levels of depressive signs the odds ratios were 2.19 (1.1 to 4.3) for mild cognitive impairment and 3.81 (1.3 to 11.5) for Alzheimer’s disease. Significant associations were also found between the separate measures of hopelessness and loneliness on the one hand and the separate outcomes of mild cognitive impairment and Alzheimer’s disease on the other. Conclusions: The results support a causal relation between depressive signs relatively early in life and cognitive function in later life. Clinical relevance includes the long-term health implications of depressive signs in midlife also for the risk of dementia.

  • 11.
    Håkansson, Krister
    et al.
    Linnéuniversitetet, Fakulteten för Hälso- och livsvetenskap (FHL), Institutionen för psykologi (PSY). Karolinska Institutet ; Stockholm University.
    Ledreux, Aurelie
    Karolinska Institutet ; Medical University of South Carolina, USA.
    Daffner, Kirk
    Harvard Medical School, USA.
    Terjestam, Yvonne
    Linnéuniversitetet, Fakulteten för Hälso- och livsvetenskap (FHL), Institutionen för psykologi (PSY).
    Bergman, Patrick
    Linnéuniversitetet, Fakulteten för samhällsvetenskap (FSV), Institutionen för idrottsvetenskap (ID).
    Carlsson, Roger
    Linnéuniversitetet, Fakulteten för Hälso- och livsvetenskap (FHL), Institutionen för psykologi (PSY).
    Kivipelto, Miia
    Karolinska Institutet.
    Granholm, Ann-Charlotte
    Medical University of South Carolina, USA.
    Mohammed, Abdul K. H.
    Linnéuniversitetet, Fakulteten för Hälso- och livsvetenskap (FHL), Institutionen för psykologi (PSY).
    BDNF Responses in Healthy Older Persons to 35 Minutes of Physical Exercise, Cognitive Training, and Mindfulness: Associations with Working Memory Function2017Ingår i: Journal of Alzheimer's Disease, ISSN 1387-2877, E-ISSN 1875-8908, Vol. 55, nr 2, s. 645-657Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Brain-derived neurotrophic factor (BDNF) has a central role in brain plasticity by mediating changes in cortical thickness and synaptic density in response to physical activity and environmental enrichment. Previous studies suggest that physical exercise can augment BDNF levels, both in serum and the brain, but no other study has examined how different types of activities compare with physical exercise in their ability to affect BDNF levels. By using a balanced cross over experimental design, we exposed nineteen healthy older adults to 35-minute sessions of physical exercise, cognitive training, and mindfulness practice, and compared the resulting changes in mature BDNF levels between the three activities. We show that a single bout of physical exercise has significantly larger impact on serum BDNF levels than either cognitive training or mindfulness practice in the same persons. This is the first study on immediate BDNF effects of physical activity in older healthy humans and also the first study to demonstrate an association between serum BDNF responsivity to acute physical exercise and working memory function. We conclude that the BDNF increase we found after physical exercise more probably has a peripheral than a central origin, but that the association between post-intervention BDNF levels and cognitive function could have implications for BDNF responsivity in serum as a potential marker of cognitive health.

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  • 12.
    Håkansson, Krister
    et al.
    Växjö universitet, Fakulteten för humaniora och samhällsvetenskap, Institutionen för samhällsvetenskap. Karolinska Institutet.
    Rovio, Suvi
    Karolinska Institutet.
    Helkala, Eeva-Liisa
    University of Kuopio, Finland.
    Vilska, Anna-Riitta
    Savonia University of Applied Sciences, Kuopio, Finland.
    Winblad, Bengt
    Karolinska Institutet.
    Soininen, Hilkka
    University of Kuopio, Finland.
    Nissinen, Aulikki
    Mohammed, Abdul K. H.
    Växjö universitet, Fakulteten för humaniora och samhällsvetenskap, Institutionen för samhällsvetenskap. Karolinska institutet.
    Kivipelto, Miia
    Karolinska institutet / University of Kuopio, Finland.
    Association between mid-life marital status and cognitive function in later life: population based cohort study2009Ingår i: BMJ. British Medical Journal, E-ISSN 1756-1833, Vol. 339, nr July, s. Article number: b2462-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    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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  • 13.
    Håkansson, Krister
    et al.
    Linnéuniversitetet, Fakultetsnämnden för hälsa, socialt arbete och beteendevetenskap, Institutionen för pedagogik, psykologi och idrottsvetenskap, PPI. Karolinska Institutet.
    Soininen, Hilkka
    University of Eastern Finland.
    Winblad, Bengt
    Karolinska Institutet.
    Mohammed, Abdul K. H.
    Linnéuniversitetet, Fakultetsnämnden för hälsa, socialt arbete och beteendevetenskap, Institutionen för pedagogik, psykologi och idrottsvetenskap, PPI.
    Kivipelto, Miia
    Karolinska Institutet.
    Feelings of hopelessness in midlife are associated with dementia risk in later life2012Ingår i: 12th International Stockholm/Springfield Symposium on Advances in Alzheimer Therapy, 2012, s. 165-165Konferensbidrag (Övrigt vetenskapligt)
    Abstract [en]

    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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    Abstract
  • 14.
    Kakooza-Mwesige, Angelina
    et al.
    Makerere Univ, Uganda;Mulago Hosp, Uganda.
    Mohammed, Abdul K. H.
    Linnéuniversitetet, Fakulteten för Hälso- och livsvetenskap (FHL), Institutionen för psykologi (PSY).
    Kristensson, Krister
    Karolinska Institutet.
    Juliano, Sharon L.
    Uniformed Serv Univ Hlth Sci, USA.
    Lutwama, Julius J.
    Uganda Virus Res Inst, Uganda.
    Emerging Viral Infections in Sub-Saharan Africa and the Developing Nervous System: A Mini Review2018Ingår i: Frontiers in Neurology, ISSN 1664-2295, E-ISSN 1664-2295, Vol. 9, artikel-id 82Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    The global public health concern is heightened over the increasing number of emerging viruses, i.e., newly discovered or previously known that have expanded into new geographical zones. These viruses challenge the health-care systems in sub-Saharan Africa (SSA) countries from which several of them have originated and been transmitted by insects worldwide. Some of these viruses are neuroinvasive, but have been relatively neglected by neuroscientists. They may provide experiments by nature to give a time window for exposure to a new virus within sizeable, previously non-infected human populations, which, for instance, enables studies on potential long-term or late-onset effects on the developing nervous system. Here, we briefly summarize studies on the developing brain by West Nile, Zika, and Chikungunya viruses, which are mosquito-borne and have spread worldwide out of SSA. They can all be neuroinvasive, but their effects vary from malformations caused by prenatal infections to cognitive disturbances following perinatal or later infections. We also highlight Ebola virus, which can leave surviving children with psychiatric disturbances and cause persistent infections in the non-human primate brain. Greater awareness within the neuroscience community is needed to emphasize the menace evoked by these emerging viruses to the developing brain. In particular, frontline neuroscience research should include neuropediatric follow-up studies in the field on long-term or late-onset cognitive and behavior disturbances or neuropsychiatric disorders. Studies on pathogenetic mechanisms for viral-induced perturbations of brain maturation should be extended to the vulnerable periods when neurocircuit formations are at peaks during infancy and early childhood.

  • 15.
    Ledreux, Aurelie
    et al.
    Univ Denver, USA.
    Håkansson, Krister
    Karolinska Univ Hosp, Sweden;Karolinska Inst, Sweden.
    Carlsson, Roger
    Linnéuniversitetet, Fakulteten för Hälso- och livsvetenskap (FHL), Institutionen för psykologi (PSY).
    Tewele, Mhretab Kidane
    Linnéuniversitetet, Fakulteten för Hälso- och livsvetenskap (FHL), Institutionen för psykologi (PSY).
    Columbo, Laura
    Med Univ South Carolina, USA.
    Terjestam, Yvonne
    Linnéuniversitetet, Fakulteten för Hälso- och livsvetenskap (FHL), Institutionen för psykologi (PSY).
    Ryan, Eliza
    Harvard Med Sch, USA.
    Tusch, Erich
    Harvard Med Sch, USA.
    Winblad, Bengt
    Karolinska Inst, Sweden.
    Daffner, Kirk
    Harvard Med Sch, USA.
    Granholm, Ann-Charlotte
    Univ Denver, USA;Med Univ South Carolina, USA;Karolinska Inst, Sweden.
    Mohammed, Abdul K. H.
    Linnéuniversitetet, Fakulteten för Hälso- och livsvetenskap (FHL), Institutionen för psykologi (PSY). Karolinska Inst, Sweden.
    Differential Effects of Physical Exercise, Cognitive Training, and Mindfulness Practice on Serum BDNF Levels in Healthy Older Adults: A Randomized Controlled Intervention Study2019Ingår i: Journal of Alzheimer's Disease, ISSN 1387-2877, E-ISSN 1875-8908, Vol. 71, nr 4, s. 1245-1261Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    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.

  • 16.
    Lindau, M.
    et al.
    Stockholm University.
    Almkvist, O.
    Stockholm University ; Karolinska Institutet.
    Mohammed, Abdul K. H.
    Linnéuniversitetet, Fakulteten för Hälso- och livsvetenskap (FHL), Institutionen för psykologi (PSY). Karolinska Institutet.
    Effects of Stress on Learning and Memory2016Ingår i: Stress: Concepts, Cognition, Emotion, and Behavior, Academic Press, 2016, s. 153-160Kapitel i bok, del av antologi (Övrigt vetenskapligt)
    Abstract [en]

    Stress activates the hypothalamus-pituitary-adrenal axis, which causes the release of glucocorticoids, a class of adrenal steroid hormones. Stress also activates the sympathetic nervous system and thereby, the release of the transmitters adrenaline and noradrenaline. Stress has a memory-modulatory effect in humans as well as in animals. In humans, the hippocampus, prefrontal cortex, and amygdala are rich in cortisol receptors. Acute and tolerable stress may increase memory performance, while excessive levels and chronic stress may have negative effects, thereby mimicking the pattern in animals. Stress in humans seems to have different effects on the various stages of memory (the memory process: encoding, consolidation, and retrieval) and can be enhanced by emotional arousal. Animals learn to associate events in their environment. Studies of the effects of manipulation of corticosterone levels in animals have helped to disentangle the influences of stress on memory and learning, and indicated that low levels enhance spatial learning, whereas higher levels impair performance. © 2016 Elsevier Inc. All rights reserved.

  • 17. Lindau, Maria
    et al.
    Lindkvist, Ove
    Mohammed, Abdul K. H.
    Växjö universitet, Fakulteten för humaniora och samhällsvetenskap, Institutionen för samhällsvetenskap.
    Effects of stress on learning and memory2007Ingår i: Encyclopedia of stress, Elsevier , 2007Kapitel i bok, del av antologi (Övrigt vetenskapligt)
  • 18.
    Porto, Fabio Henrique de Gobbi
    et al.
    Harvard University, USA.
    Fox, Anne Murphy
    Harvard University, USA.
    Tusch, Erich S.
    Harvard University, USA.
    Sorond, Farzaneh
    Harvard University, USA.
    Mohammed, Abdul K. H.
    Linnéuniversitetet, Fakulteten för Hälso- och livsvetenskap (FHL), Institutionen för psykologi (PSY). Karolinska Institutet.
    Daffner, Kirk R.
    Harvard University, USA.
    In vivo evidence for neuroplasticity in older adults2015Ingår i: Brain Research Bulletin, ISSN 0361-9230, E-ISSN 1873-2747, Vol. 114, s. 56-61Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Neuroplasticity can be conceptualized as an intrinsic property of the brain that enables modification of function and structure in response to environmental demands. Neuroplastic strengthening of synapses is believed to serve as a critical mechanism underlying learning, memory, and other cognitive functions. Ex vivo work investigating neuroplasticity has been done on hippocampal slices using high frequency stimulation. However, in vivo neuroplasticity in humans has been difficult to demonstrate. Recently, a long-term potentiation-like phenomenon, a form of neuroplastic change, was identified in young adults by differences in visual evoked potentials (VEPs) that were measured before and after tetanic visual stimulation (TVS). The current study investigated whether neuroplastic changes in the visual pathway can persist in older adults. Seventeen healthy subjects, 65 years and older, were recruited from the community. Subjects had a mean age of 77.4 years, mean education of 17 years, mean MMSE of 29.1, and demonstrated normal performance on neuropsychological tests. 1 Hz checkerboard stimulation, presented randomly to the right or left visual hemi-field, was followed by 2 mm of 9 Hz stimulation (TVS) to one hemi-field. After 2 mm of rest, 1 Hz stimulation was repeated. Temporospatial principal component analysis was used to identify the Nib component of the VEPs, at lateral occipital locations, in response to 1 Hz stimulation pre- and post-TVS. Results showed that the amplitude of factors representing the early and late Nib component was substantially larger after tetanic stimulation. These findings indicate that high frequency visual stimulation can enhance the Nib in cognitively high functioning old adults, suggesting that neuroplastic changes in visual pathways can continue into late life. Future studies are needed to determine the extent to which this marker of neuroplasticity is sustained over a longer period of time, and is influenced by age, cognitive status, and neurodegenerative disease. (C) 2015 Elsevier Inc. All rights reserved.

  • 19.
    Simon, Sharon S.
    et al.
    Harvard Med Sch, USA.
    Tusch, Erich S.
    Harvard Med Sch, USA.
    Feng, Nicole C.
    Harvard Med Sch, USA.
    Håkansson, Krister
    Linnéuniversitetet, Fakulteten för Hälso- och livsvetenskap (FHL), Institutionen för psykologi (PSY). Karolinska Institutet.
    Mohammed, Abdul K. H.
    Linnéuniversitetet, Fakulteten för Hälso- och livsvetenskap (FHL), Institutionen för psykologi (PSY). Karolinska Institutet.
    Daffner, Kirk R.
    Harvard Med Sch, USA.
    Is Computerized Working Memory Training Effective in Healthy Older Adults?: Evidence from a Multi-Site, Randomized Controlled Trial2018Ingår i: Journal of Alzheimer's Disease, ISSN 1387-2877, E-ISSN 1875-8908, Vol. 65, nr 3, s. 931-949Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Developing effective interventions to attenuate age-related cognitive decline and prevent or delay the onset of dementia are major public health goals. Computerized cognitive training (CCT) has been marketed increasingly to older adults, but its efficacy remains unclear. Working memory (WM), a key determinant of higher order cognitive abilities, is susceptible to age-related decline and a relevant target for CCT in elders. Objective: To evaluate the efficacy of CCT focused on WM compared to an active control condition in healthy older adults. Methods: Eighty-two cognitively normal adults from two sites (USA and Sweden) were randomly assigned to Cogmed Adaptive or Non-Adaptive (active control) CCT groups. Training was performed in participants' homes, five days per week over five weeks. Changes in the performance of the Cogmed trained tasks, and in five neuropsychological tests (Trail Making Test Part A and Part B, Digit Symbol, Controlled Oral Word Association Test and Semantic Fluency) were used as outcome measures. Results: The groups were comparable at baseline. The Adaptive group showed robust gains in the trained tasks, and there was a time-by-group interaction for the Digit Symbol test, with significant improvement only after Adaptive training. In addition, the magnitude of the intervention effect was similar at both sites. Conclusion: Home-based CCT Adaptive WM training appears more effective than Non-Adaptive training in older adults from different cultural backgrounds. We present evidence of improvement in trained tasks and on a demanding untrained task dependent upon WM and processing speed. The benefits over the active control group suggest that the Adaptive CCT gains were linked to providing a continuously challenging level of WM difficulty.

  • 20.
    Tusch, Erich S.
    et al.
    Harvard Med Sch, USA.
    Alperin, Brittany R.
    Oregon Hlth & Sci Univ, USA.
    Ryan, Eliza
    Harvard Med Sch, USA.
    Holcomb, Phillip J.
    Tufts Univ, USA.
    Mohammed, Abdul K. H.
    Linnéuniversitetet, Fakulteten för Hälso- och livsvetenskap (FHL), Institutionen för psykologi (PSY). Karolinska Institutet.
    Daffner, Kirk R.
    Harvard Med Sch, USA.
    Changes in Neural Activity Underlying Working Memory after Computerized Cognitive Training in Older Adults2016Ingår i: Frontiers in Aging Neuroscience, ISSN 1663-4365, E-ISSN 1663-4365, Vol. 8, artikel-id 255Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Computerized cognitive training (CCT) may counter the impact of aging on cognition, but both the efficacy and neurocognitive mechanisms underlying CCT remain controversial. In this study, 35 older individuals were randomly assigned to Cogmed adaptive working memory (WM) CCT or an active control CCT, featuring five weeks of five similar to 40 min sessions per week. Before and after the 5-week intervention, event-related potentials were measured while subjects completed a visual n-back task with three levels of demand (0-back, 1-back, 2-back). The anterior P3a served as an index of directing attention and the posterior P3b as an index of categorizationNVM updating. We hypothesized that adaptive CCT would be associated with decreased P3 amplitude at low WM demand and increased P3 amplitude at high WM demand. The adaptive CCT group exhibited a training-related increase in the amplitude of the anterior P3a and posterior P3b in response to target stimuli across n-back tasks, while subjects in the active control CCT group demonstrated a post-training decrease in the anterior P3a. Performance did not differ between groups or sessions. Larger overall P3 amplitudes were strongly associated with better task performance. Increased post-CCT P3 amplitude correlated with improved task performance; this relationship was especially robust at high task load. Our findings suggest that adaptive WM training was associated with increased orienting of attention, as indexed by the P3a, and the enhancement of categorization/WM updating processes, as indexed by the P3b. Increased P3 amplitude was linked to improved performance; however. there was no direct association between adaptive training and improved performance.

  • 21. Zhu, Shun-Wei
    et al.
    Codita, Alina
    Bogdanovic, Nenad
    Hjerling-Leffler, Jens
    Ernfors, Patrik
    Winblad, Bengt
    Dickins, David W.
    Mohammed, Abdul K. H.
    Växjö universitet, Fakulteten för humaniora och samhällsvetenskap, Institutionen för samhällsvetenskap. Alzheimer's Disease Research Center, NVS Department, Karolinska Institutet, Stockholm 141 86, Sweden.
    Influence of environmental manipulation on exploratory behaviour in male BDNF knockout mice2009Ingår i: Behavioural Brain Research, ISSN 0166-4328, E-ISSN 1872-7549, Vol. 197, nr 2, s. 339-346Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    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.

  • 22. Zhu, Shun-Wei
    et al.
    Yee, Benjamin K
    Nyffeler, Myriel
    Winblad, Bengt
    Feldon, Joram
    Mohammed, Abdul K. H.
    Växjö universitet, Fakulteten för humaniora och samhällsvetenskap, Institutionen för samhällsvetenskap.
    Influence of differential housing on emotional behaviour and neurotrophin levels in mice.2006Ingår i: Behav Brain Res, ISSN 0166-4328, Vol. 169, nr 1, s. 10-20Artikel i tidskrift (Övrigt vetenskapligt)
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