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  • Backman, Lars, et al. (författare)
  • Striatal dopamine D2 binding is related to frontal BOLD response during updating of long-term memory representations.
  • 2009
  • Ingår i: NeuroImage. - 1053-8119. ; 46:4, s. 1194-1199
  • Tidskriftsartikel (refereegranskat)abstract
    • Multi-modal brain imaging was used to examine the relation between individual differences in resting-state striatal dopamine D2 binding and the magnitude of prefrontal BOLD activation during updating of long-term memory (LTM) representations. Increased activity in the left prefrontal cortex was observed when LTM updating was required, and there was a positive correlation between striatal D2 activity and the magnitude of left prefrontal activity during updating. These findings support predictions from neurocomputational models of a relation of dopaminergic neurotransmission to transient cognitive operations and related brain activity.
  • Backman, Lars, et al. (författare)
  • Influence of COMT gene polymorphism on fMRI-assessed sustained and transient activity during a working memory task.
  • 2010
  • Ingår i: Journal of cognitive neuroscience. - Cambridge, Mass. : Published by the MIT Press with the Cognitive Neuroscience Institute. - 0898-929X. ; 22:7, s. 1614-1622
  • Tidskriftsartikel (refereegranskat)abstract
    • The catechol O-methyltransferase (COMT) gene--encoding an enzyme that is essential for the degradation of dopamine (DA) in prefrontal cortex (PFC)--contains a single nucleotide polymorphism (val/met) important for cognition. According to the tonic-phasic hypothesis, individuals carrying the low-enzyme-activity allele (met) are characterized by enhanced tonic DA activity in PFC, promoting sustained cognitive representations in working memory. Val carriers have reduced tonic but enhanced phasic dopaminergic activity in subcortical regions, enhancing cognitive flexibility. We tested the tonic-phasic DA hypothesis by dissociating sustained and transient brain activity during performance on a 2-back working memory test using mixed blocked/event-related functional magnetic resonance imaging. Participants were men recruited from a random sample of the population (the Betula study) and consisted of 11 met/met and 11 val/val carriers aged 50 to 65 years, matched on age, education, and cognitive performance. There were no differences in 2-back performance between genotype groups. Met carriers displayed a greater transient medial temporal lobe response in the updating phase of working memory, whereas val carriers showed a greater sustained PFC activation in the maintenance phase. These results support the tonic-phasic theory of DA function in elucidating the specific phenotypic influence of the COMT val(158)met polymorphism on different components of working memory.
  • Lind, Johanna, et al. (författare)
  • Reduced functional brain activity response in cognitively intact apolipoprotein E ε4 carriers
  • 2006
  • Ingår i: Brain. - Oxford University Press. - 0006-8950. ; 129:5, s. 1240-1248
  • Tidskriftsartikel (refereegranskat)abstract
    • The apolipoprotein E epsilon4 (APOE epsilon4) is the main known genetic risk factor for Alzheimer's disease. Genetic assessments in combination with other diagnostic tools, such as neuroimaging, have the potential to facilitate early diagnosis. In this large-scale functional MRI (fMRI) study, we have contrasted 30 APOE epsilon4 carriers (age range: 49-74 years; 19 females), of which 10 were homozygous for the epsilon4 allele, and 30 non-carriers with regard to brain activity during a semantic categorization task. Test groups were closely matched for sex, age and education. Critically, both groups were cognitively intact and thus symptom-free of Alzheimer's disease. APOE epsilon4 carriers showed reduced task-related responses in the left inferior parietal cortex, and bilaterally in the anterior cingulate region. A dose-related response was observed in the parietal area such that diminution was most pronounced in homozygous compared with heterozygous carriers. In addition, contrasts of processing novel versus familiar items revealed an abnormal response in the right hippocampus in the APOE epsilon4 group, mainly expressed as diminished sensitivity to the relative novelty of stimuli. Collectively, these findings indicate that genetic risk translates into reduced functional brain activity, in regions pertinent to Alzheimer's disease, well before alterations can be detected at the behavioural level.
  • Lind, Johanna, et al. (författare)
  • Reduced hippocampal volume in non-demented carriers fo the apolipoprotein E ε4 : Relation to chronological age and recognition memory
  • 2006
  • Ingår i: Neuroscience Letters. - 0304-3940. ; 396:1, s. 23-27
  • Tidskriftsartikel (refereegranskat)abstract
    • Apolipoprotein E ε4 (APOE ε4) is the main known genetic risk factor for Alzheimer's disease (AD). Some previous studies have reported structural brain changes as well as cognitive deficits in non-demented APOE ε4 carriers, but the pattern of results is inconsistent and studies with larger sample sizes have been called for. Here we compared hippocampal volume and recognition–memory performance between AD-symptom-free carriers (N = 30) and non-carriers (N = 30) of the APOE ε4 (age range: 49–79 years). We observed reduced right hippocampal volume in APOE ε4 carriers, and found that the difference was most pronounced before the age of 65. Further, the APOE ε4 carriers made significantly more false alarms in the recognition–memory test, and the number of false alarms correlated significantly with right hippocampus volume. These results indicate that relatively young individuals at genetic risk for AD have smaller hippocampal volume and lower performance on hippocampal-dependent cognitive tasks. A question for the future is whether smaller hippocampal volume represents early-onset hippocampal volume reduction or an inherent trait.
  • Nylander, Ruta, et al. (författare)
  • Relation between Cardiovascular Disease Risk Markers and Brain Infarcts Detected by Magnetic Resonance Imaging in an Elderly Population
  • 2014
  • Ingår i: Journal of Stroke & Cerebrovascular Diseases. - 1052-3057.
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND:Established cardiovascular risk markers, such as hypertension, are associated with increased risk of brain infarcts. The newer markers N-terminal pro-brain natriuretic peptide, troponin I, C-reactive protein, and cystatin C may affect the risk of cardiovascular events and potentially, thereby, also stroke. We investigated the association between established and new risk markers for cardiovascular disease and brain infarcts detected by magnetic resonance imaging (MRI) at age 75.METHODS:Four hundred six randomly selected subjects from the Prospective Investigation of the Vasculature in Uppsala Seniors study were examined with MRI of the brain at age 75. Blood samples, measurements, and dedicated questionnaires at age 70 were used for analysis of risk markers. A history of diseases had been obtained at age 70 and 75. MRI was evaluated regarding lacunar and cortical infarcts. Univariate associations between outcomes and risk markers were assessed with logistic regression models.RESULTS:One or more infarcts were seen in 23% of the subjects (20% had only lacunar infarcts, 1% had only cortical infarcts, and 2% had both). Hypertension (odds ratio [OR] 2.6, 95% confidence interval [CI] 1.4, 4.7) and obesity (OR 1.3; CI 1.0, 1.8) were significantly associated with increased risk of brain infarction. The newer risk markers were not significantly associated with the brain infarcts.CONCLUSIONS:The new markers were not associated with the predominantly lacunar infarcts in our 75-year-old population, why troponin I and NT-proBNP may be associated mainly with cardioembolic infarcts as shown recently.
  • Farde, Lars, et al. (författare)
  • Age-related loss of olfactory sensitivity : Association to dopamine transporter binding in putamen
  • 2009
  • Ingår i: Neuroscience. - Elsevier Ltd.. - 0306-4522. ; 161:2, s. 422-426
  • Tidskriftsartikel (refereegranskat)abstract
    • The relationship between age-related reductions in the binding potential for the striatal dopamine transporter (DAT) and age-related deficits in olfactory sensitivity was examined in 12 subjects ranging from 36 to 82 years of age. Positron emission tomography (PET) and the radioligand [11C]β-CIT-FE were used to determine DAT binding in two striatal regions, the caudate and the putamen. The results showed age-related losses of DAT binding from early to late adulthood of similar size for caudate and putamen, and there was a pronounced age deterioration in olfactory sensitivity. Importantly, the age-related olfactory deficit was associated with reductions in DAT binding in putamen, but not caudate. Also, DAT binding in putamen added systematic variance in odor threshold after controlling for age. The findings indicate that DAT binding in putamen is related to age-related olfactory deficits, as well as to odor sensitivity independently of age.
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