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  • 1.
    Behrens, Anders
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap. Blekinge Centre of Competence, Blekinge Hospital Karlskrona, Karlskrona, Sweden.
    Eklund, Anders
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Centrum för medicinsk teknik och fysik (CMTF). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Elgh, Eva
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Smith, Cynthia
    Williams, Michael A
    Malm, Jan
    A computerized neuropsychological test battery designed for idiopathic normal pressure hydrocephalus2014Ingår i: Fluids and Barriers of the CNS, ISSN 2045-8118, E-ISSN 2045-8118, Vol. 11, artikel-id 22Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: A tool for standardized and repeated neuropsychological assessments in patients with idiopathic normal pressure hydrocephalus (INPH) is needed. The objective of this study was to develop a computerized neuropsychological test battery designed for INPH and to evaluate its reliability, validity and patient's ability to complete the tests.

    METHODS: Based on a structured review of the literature on neuropsychological testing in INPH, the eight tests most sensitive to the INPH cognitive profile were implemented in a computerized format. The Geriatric Depression Scale (GDS) was also included. Tests were presented on a touch-screen monitor, with animated instructions and speaker sound. The battery was evaluated with the following cohorts: A. Test-retest reliability, 44 healthy elderly; B. Validity against standard pen and pencil testing, 28 patients with various cognitive impairments; C. Ability to complete test battery, defined as completion of at least seven of the eight tests, 40 investigated for INPH.

    RESULTS: A. All except the figure copy test showed good test-retest reliability, r = 0.67-0.90; B. A high correlation was seen between conventional and computerized tests (r = 0.66-0.85) except for delayed recognition and figure copy task; C. Seventy-eight percent completed the computerized battery; Patients diagnosed with INPH (n = 26) performed worse on all tests, including depression score, compared to healthy controls.

    CONCLUSIONS: A new computerized neuropsychological test battery designed for patients with communicating hydrocephalus and INPH was introduced. Its reliability, validity for general cognitive impairment and completion rate for INPH was promising. After exclusion of the figure copy task, the battery is ready for clinical evaluation and as a next step we suggest validation for INPH and a comparison before and after shunt surgery.

    TRIAL REGISTRATION: ClinicalTrials.org NCT01265251.

  • 2.
    Bäckström, David
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Eriksson Domellöf, Magdalena
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Granåsen, Gabriel
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa.
    Linder, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Mayans, Sofia
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi.
    Elgh, Eva
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi.
    Jakobson Mo, Susanna
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Forsgren, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    PITX3 genotype and risk of dementia in Parkinson's disease: A population-based study2017Ingår i: Journal of the Neurological Sciences, ISSN 0022-510X, E-ISSN 1878-5883, Vol. 381, s. 278-284Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Dementia is a devastating manifestation of Parkinson's disease (PD). This study investigates whether a common polymorphism in the PITX3 gene (rs2281983), which is of importance for the function of dopaminergic neurons, affects the risk of developing dementia in PD and whether it affects dopamine transporter (DAT) uptake. We PITX3 genotyped 133 patients with new-onset, idiopathic PD, participating in a population-based study in Sweden. Patients were followed prospectively during 6-11 years with extensive investigations, including neuropsychology and DAT-imaging with I-123 FP-CIT. The primary outcome was the incidence of PD dementia (PDD), diagnosed according to published criteria, studied by the Kaplan-Meier method and Cox proportional hazards. Performance in individual cognitive domains, the incidence of visual hallucinations, disease progression and striatal DAT uptake on imaging was also investigated. PD patients carrying the PITX3 C allele had an increased risk of developing PDD (hazard ratio: 2.87, 95% CI: 1.42-5.81, p = 0.003), compared to the PD patients homozygous for the T-allele. Furthermore, the PITX3 C allele carriers with PD had a poorer cognitive performance in the visuospatial domain (p < 0.001) and a higher incidence of visual hallucinations. A trend towards a lower striatal DAT uptake in the PITX3 C allele carriers was suggested, but could not be confirmed. Our results show that a common polymorphism in the PITX3 gene affects the risk of developing PDD and visuospatial dysfunction in idiopathic PD. If validated, these findings can provide new insights into the neurobiology and genetics of non-motor symptoms in PD.

  • 3.
    Bäckström, David
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Eriksson Domellöf, Magdalena
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Granåsen, Gabriel
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa.
    Linder, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Mayans, Sofia
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi.
    Elgh, Eva
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi.
    Zetterberg, H.
    Blennow, K.
    Forsgren, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Farmakologi.
    Polymorphisms in dopamine-associated genes and cognitive decline in Parkinson's disease2018Ingår i: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 137, nr 1, s. 91-98Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objectives: Cognitive decline is common in Parkinson's disease (PD), but the underlying mechanisms for this complication are incompletely understood. Genotypes affecting dopamine transmission may be of importance. This study investigates whether genotypes associated with reduced prefrontal dopaminergic tone and/or reduced dopamine D2-receptor availability (Catechol-O-methyltransferase [COMT] Val(158)Met genotype and DRD2 (CT)-T-957 genotype) affect the development of cognitive deficits in PD.

    Materials and methods: One hundred and 34 patients with idiopathic PD, participating in a regional, population-based study of incident parkinsonism, underwent genotyping. After extensive baseline investigations (including imaging and biomarker analyses), the patients were followed prospectively during 6-10 years with neuropsychological evaluations, covering six cognitive domains. Cognitive decline (defined as the incidence of either Parkinson's disease mild cognitive impairment [PD-MCI] or dementia [PDD], diagnosed according to published criteria and blinded to genotype) was studied as the primary outcome.

    Results: Both genotypes affected cognition, as shown by Cox proportional hazards models. While the COMT(158)Val/Val genotype conferred an increased risk of mild cognitive impairment in patients with normal cognition at baseline (hazard ratio: 2.13, P=.023), the DRD2(957)T/T genotype conferred an overall increased risk of PD dementia (hazard ratio: 3.22, P<.001). The poorer cognitive performance in DRD2(957)T/T carriers with PD occurred mainly in episodic memory and attention.

    Conclusions: The results favor the hypothesis that dopamine deficiency in PD not only relate to mild cognitive deficits in frontostriatal functions, but also to a decline in memory and attention. This could indicate that dopamine deficiency impairs a wide network of brain areas.

  • 4.
    Degerman, Sofie
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Domellöf, Magdalena
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Landfors, Mattias
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Linder, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Lundin, Mathias
    Umeå universitet, Samhällsvetenskapliga fakulteten, Handelshögskolan vid Umeå universitet, Statistik.
    Haraldsson, Susann
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Elgh, Eva
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Roos, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Forsgren, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Long Leukocyte Telomere Length at Diagnosis Is a Risk Factor for Dementia Progression in Idiopathic Parkinsonism2014Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, nr 12, artikel-id e113387Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Telomere length (TL) is regarded as a marker of cellular aging due to the gradual shortening by each cell division, but is influenced by a number of factors including oxidative stress and inflammation. Parkinson's disease and atypical forms of parkinsonism occur mainly in the elderly, with oxidative stress and inflammation in afflicted cells. In this study the relationship between blood TL and prognosis of 168 patients with idiopathic parkinsonism (136 Parkinson's disease [PD], 17 Progressive Supranuclear Palsy [PSP], and 15 Multiple System Atrophy [MSA]) and 30 controls was investigated. TL and motor and cognitive performance were assessed at baseline (diagnosis) and repeatedly up to three to five years follow up. No difference in TL between controls and patients was shown at baseline, nor any significant difference in TL stability or attrition during follow up. Interestingly, a significant relationship between TL at diagnosis and cognitive phenotype at follow up in PD and PSP patients was found, with longer mean TL at diagnosis in patients that developed dementia within three years.

  • 5.
    Domellof, Magdalena Eriksson
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Elgh, Eva
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering.
    Forsgren, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    The relation between cognition and motor dysfunction in drug-naive newly diagnosed patients with parkinson's disease2011Ingår i: Movement Disorders, ISSN 0885-3185, E-ISSN 1531-8257, Vol. 26, nr 12, s. 2183-2189Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Recent studies have reported cognitive decline to be common in the early phase of Parkinson's disease. Imaging data connect working memory and executive functioning to the dopamine system. It has also been suggested that bradykinesia is the clinical manifestation most closely related to the nigrostriatal lesion. Exploring the relationship between motor dysfunction and cognition can help us find shared or overlapping systems serving different functions. This relationship has been sparsely investigated in population-based studies of untreated Parkinson's disease. The aim of the present study was to investigate the association between motor signs and cognitive performance in the early stages of Parkinson's disease before the intake of dopaminergic medication. Patients were identified in a population-based study of incident cases with idiopathic parkinsonism. Patients with the postural instability and gait disturbances phenotype were compared with patients with the tremor-dominant phenotype on demographics and cognitive measures. Associations between cognitive and motor scores were investigated, with age, education, and sex controlled for. Bradykinesia was associated with working memory and mental flexibility, whereas axial signs were associated with episodic memory and visuospatial functioning. No significant differences in the neuropsychological variables were found between the postural instability and gait disturbances phenotype and the tremor phenotype. Our results indicate a shared system for slow movement and inflexible thinking that may be controlled by a dopaminergic network different from dopaminergic networks involved in tremor and/or rigidity. The association between axial signs and memory and visuospatial function may point to overlapping systems or pathologies related to these abilities.

    (C) 2011 Movement Disorder Society

  • 6.
    Domellöf, Magdalena E
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Ekman, Urban
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB). Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Forsgren, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Elgh, Eva
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Cognitive function in the early phase of Parkinson's disease, a five-year follow-up2015Ingår i: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 132, nr 2, s. 79-88Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Presence of mild cognitive impairment (MCI) as a predictor for Parkinson's disease dementia (PDD) has been discussed from a clinical perspective. Recently, a Movement Disorder Society (MDS) commissioned Task Force published guidelines for PD-MCI. However, long-term follow-ups of the PD-MCI guidelines for the prediction of PDD have been sparse.

    METHOD: In a community-based cohort of PD, the MDS guidelines for PD-MCI and consensus criteria for PDD were applied on 147 subjects. The predictive ability of PD-MCI for PDD was investigated. Additionally, baseline comparisons were conducted between MCI that converted to PDD and those who did not, and evolvement of motor function was investigated.

    RESULTS: One fourth of the population developed PDD. MCI and age at baseline predicted later occurrence of PDD, and baseline results of tests measuring episodic memory, visuospatial function, semantic fluency, and mental flexibility differed between MCI converters and non-converters. Postural instability/gait (PIGD) phenotype and education did not predict later occurrence of PDD, but increased postural/gait disturbances were shown across time in those developing dementia.

    CONCLUSION: The new PD-MCI guidelines are useful to detect patients at risk for developing PDD. The PIGD phenotype at diagnosis was not a predictor of PDD within 5 years, but the study supports a temporal association between postural/gait disturbances and PDD. Older patients with PD-MCI at baseline with decline in episodic memory, semantic fluency, and mental flexibility need to be carefully monitored regarding cognition and likely also for fall risk.

  • 7.
    Domellöf, Magdalena E
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Forsgren, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Elgh, Eva
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Persistence of associations between cognitive impairment and motor dysfunction in the early phase of Parkinson's disease2013Ingår i: Journal of Neurology, ISSN 0340-5354, E-ISSN 1432-1459, Vol. 260, nr 9, s. 2228-2236Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The relation between cognitive and motor functions in Parkinson's disease is not fully understood. In an incidence population of newly diagnosed drug na < ve patients with Parkinson's disease, associations were found between the degree of bradykinesia and postural instability and gait disturbances, measured by the Unified Disease Rating Scale, and different types of cognitive functions. To investigate the stability of these associations over time, we explored the association of differences between baseline and 1-year follow-up in 91 incident cases with Parkinson's disease. The magnitude of change between the two assessments was assessed together with analysis of differences based on which dopaminergic medication was used. Change in bradykinesia was associated with change in working memory and mental flexibility. Changes in postural instability and gait disturbances were associated with change in visuospatial memory. A negative effect of the dopamine agonist pramipexole on phonemic fluency performance was found compared to treatment with other dopaminergic drugs. Change in cognitive and motor functions were associated from time of diagnosis until 1 year after diagnosis. These persisting findings strengthen results from a previous cross-sectional study suggesting similar associations. The effects of dopamine agonists on phonemic fluency should be investigated further.

  • 8.
    Domellöf, Magdalena
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Forsgren, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Ekman, Urban
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi.
    Elgh, Eva
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Cognitive function in the early phase of Parkinson's disease, a longitudinal follow-upManuskript (preprint) (Övrigt vetenskapligt)
  • 9.
    Ekman, Urban
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi. Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Eriksson, Johan
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Forsgren, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Domellöf, Magdalena
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Elgh, Eva
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Lundquist, Anders
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Samhällsvetenskapliga fakulteten, Handelshögskolan vid Umeå universitet, Statistik.
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi. Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Longitudinal changes in task-evoked brain responses in Parkinson's disease patients with and without mild cognitive impairment2014Ingår i: Frontiers in Neuroscience, ISSN 1662-4548, E-ISSN 1662-453X, Vol. 8, artikel-id 207Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Cognitive deficits are common in Parkinson's disease. Previous cross-sectional research has demonstrated a link between cognitive impairments and fronto-striatal dopaminergic dysmodulation. However, longitudinal studies that link disease progression with altered task-evoked brain activity are lacking. Therefore, our objective was to longitudinally evaluate working-memory related brain activity changes in Parkinson's disease patients with and without mild cognitive impairment (MCI). Patients were recruited within a longitudinal cohort study of incident patients with idiopathic parkinsonism. We longitudinally (at baseline examination and at 12-months follow-up) compared 28 patients with Parkinson's disease without MCI with 11 patients with Parkinson's disease and MCI. Functional MRI blood oxygen level dependent signal was measured during a verbal two-back working-memory task. Patients with MCI under-recruited bilateral medial prefrontal cortex at both time-points (main effect of group: p < 0.001, uncorrected). Critically, a significant group-by-time interaction effect (p < 0.001, uncorrected) was found in the right fusiform gyrus, indicating that working-memory related activity decreased for patients with Parkinson's disease and MCI between baseline and follow-up, while patients without MCI were stable across time-points. The functional connectivity between right fusiform gyrus and bilateral caudate nucleus was stronger for patients without MCI relative to patients with MCI. Our findings support the view that deficits in working-memory updating are related to persistent fronto-striatal under-recruitments in patients with early phase Parkinson's disease and MCI. The longitudinal evolution of MCI in Parkinson's disease translates into additional task-evoked posterior cortical changes.

  • 10.
    Elgh, Eva
    Umeå universitet, Medicinsk fakultet, Samhällsmedicin och rehabilitering, Geriatrik.
    Neuropsychological Function in Relation to Structural and Functional Brain Changes in Alzheimer’s Disease2004Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    The aim of this doctoral thesis was to study neuropsychological function in relation to structural and functional brain changes in Alzheimer´s disease (AD).

    In the first study relations between hippocampal volume, neuropsychological function and limbic-hypothalamic-pituitary-adrenal (LHPA) axis disturbances in AD were investigated with magnetic resonance imaging (MRI). Reduced hippocampal CA1 volume and suppressed cortisol levels in combination, best predicted the variation in neuropsychological performance. The conclusion was that reduced hippocampal volume and LHPA axis disturbances are associated to level of cognitive function in AD.

    The second study focused on whether patients with early AD showed an altered regional cerebral blood flow (rCBF) pattern compared to control persons, correlation between performance on memory tests and rCBF in sub-lobar volumes of the brain were investigated. The rCBF was measured with single photon emission computed tomography (SPECT). AD-patients showed a significantly lower rCBF in temporoparietal regions including left hippocampus compared to controls. The diagnostic sensitivity and specificity for AD was high in temporoparietal regions. AD-patients had significantly lower performance on semantic and, in particular, episodic memory-tests compared to the controls, and their performance on several episodic tests correlated with rCBF in parietal and temporal regions including left hippocampus, which suggest that abnormalities in the rCBF pattern underlie impaired episodic memory functioning in AD. The conclusion was that an observer-independent analyzing method for SPECT with sub-lobar volumes VOI´s is promising in the diagnosis of AD.

    In a third study possible differences in memory-related functional brain activation between persons with high versus low risk for AD were examined with functional magnetic resonance imaging (fMRI). The high-risk individuals performed worse than low-risk individuals on tests of episodic memory. Patterns of brain activity during episodic encoding and retrieval showed significant group differences. During both encoding and retrieval, the low-risk persons showed increased activity relative to a baseline condition in prefrontal and hippocampal brain regions that previously have been implicated in episodic memory. By contrast, the high-risk persons did not significantly activate any prefrontal regions, but instead showed increased activity in visual occipito-temporal regions. The conclusion was that patterns of prefrontal brain activity related to episodic memory differed between persons with high versus low risk for AD, and lowered prefrontal activity may predict subsequent disease.

    In a final study SPECT was used to map patterns of rCBF in an activated state (an episodic encoding task) and in a rest condition in persons with mild AD and in healthy elderly control persons. A reduction of rCBF in temporoparietal regions that was more pronounced in mild AD in the activated encoding task was observed. The conclusion was that there are rCBF differences between mild AD patients and healthy controls in temporoparietal regions, and the temporoparietal reduction is more pronounced during activation than during rest which might be important in the early diagnosis of AD.

    Taken together, these findings show that level of neuropsychological function, notably episodic memory, can be systematically related to functional disturbances in the LHPA axis and to the function of temporoparietal and prefrontal brain regions in AD patients. These changes are detectable in patients with risk for AD and in an early phase of AD which suggests that the obtained results might be important for early diagnosis of AD.

  • 11.
    Elgh, Eva
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Domellöf, Magdalena
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik. Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Linder, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Edström, Mona
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Stenlund, Hans
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa.
    Forsgren, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Cognitive function in early Parkinson's disease: a population-based study2009Ingår i: European Journal of Neurology, ISSN 1351-5101, E-ISSN 1468-1331, Vol. 16, nr 12, s. 1278-1284Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND AND PURPOSE: The study aims to describe the frequency, pattern and determinants of cognitive function in patients with newly diagnosed Parkinson's disease (PD); to compare patients with impaired cognition to patients with intact cognition; and to compare to matched healthy controls.

    METHODS: Patients were identified in a longitudinal population based study of idiopathic non-drug induced parkinsonism. Eighty-eight newly diagnosed patients with PD and no dementia were included during a four year period. The patients and 30 age- and sex-matched healthy control subjects underwent a comprehensive neuropsychological assessment.

    RESULTS: Patients performed significantly worse than healthy controls in a majority of neuropsychological tests. Test results in attention, psychomotor function, episodic memory (free recall), executive function and category fluency were significantly lower in the patient group. Comparison with normative data revealed that 30% of the patients had deficits in > or =1 cognitive domain (episodic memory, executive function and verbal function). Seventy per cent of the patients had normal performance. Unified Parkinson's Disease Rating Scale (UPDRS) III sub scores; speech, facial expression, rigidity and bradykinesia were significantly higher, and disease duration shorter amongst the cognitively impaired than amongst the cognitively intact patients. Tremor showed no difference. Education level was an independent predictor of dysfunction in patients with > or =2 cognitive domains affected.

    CONCLUSION: Cognitive dysfunction is common in untreated patients in early PD, affecting attention, psychomotor function, episodic memory, executive function and category fluency. Education level was an independent predictor of severe cognitive dysfunction.

  • 12.
    Elgh, Eva
    et al.
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi.
    Hu, Xiaolei
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering.
    Dynamic Trajectory of Long-Term Cognitive Improvement Up to 10 Years in Young Community-Dwelling Stroke Survivors: A Cohort Study2019Ingår i: Frontiers in Neurology, ISSN 1664-2295, E-ISSN 1664-2295, Vol. 10, artikel-id 97Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background and objective: The trajectories of long-term and domain-specific cognitive alterations over a decade after stroke are largely unknown. This study aims to investigate the dynamic alterations of domain-specific cognitive performance among young stroke survivors over 10 years after their first stroke.

    Methods: A prospective cohort study was carried out on 38 young stroke survivors (aged 18-65 at stroke onset) living in the community at 10 years after their first stroke. The cognitive outcomes were assessed repeatedly at 1 week, 7 months, and 10 years after their first stroke on the sub-domains: process speed (Symbol search and Coding from WAIS, TMT-A), visual attention (Bells test), visuospatial function (Block design from WAIS, RCFT), executive function (TMT-B, verbal fluency), verbal function [Letter fluency (FAS) from D-KEFS and CD], working memory (Digit Span from WAIS), immediate memory (RCFT and CD), and delayed memory (RCFT and CD). Global cognition was evaluated with Mini mental state examination at the two later time-points.

    Results: We found a delayed significant improvement of working memory with total recovery 10 years after participants' stroke. Visuospatial function recovered already at 7 months and remained stable at 10-year follow-up. Process speed demonstrated a significant decrease at 10 years compared to 7 months after stroke onset, a decrease which could be compensated by enhancements of other cognitive domains. No further deterioration was found in verbal function, immediate-, and delayed memory, and executive function during 10-year follow-up. Global cognition improved by on average two points between 7 months and 10 years. Education level and fatigue showed low to moderate positive correlations with cognitive improvements.

    Conclusions: The concordance of cognitive improvements between domain-specific and global cognitions strongly suggest that some young stroke survivors do improve their cognitive outcome over a 10-year period following their first stroke. This finding fills a gap of knowledge with respect to the dynamic trajectory of post-stroke cognition, with important implications in clinical practice.

  • 13.
    Elgh, Eva
    et al.
    Umeå universitet, Medicinsk fakultet, Samhällsmedicin och rehabilitering, Geriatrik.
    Lindqvist Åstot, Ann
    Umeå universitet, Medicinsk fakultet, Samhällsmedicin och rehabilitering, Geriatrik.
    Fagerlund, Markku
    Umeå universitet, Medicinsk fakultet, Strålningsvetenskaper.
    Eriksson, Sture
    Umeå universitet, Medicinsk fakultet, Samhällsmedicin och rehabilitering, Geriatrik.
    Olsson, Tommy
    Umeå universitet, Medicinsk fakultet, Folkhälsa och klinisk medicin, Medicin.
    Näsman, Birgitta
    Umeå universitet, Medicinsk fakultet, Samhällsmedicin och rehabilitering.
    Cognitive dysfunction, hippocampal atrophy and glucocorticoid feedback in Alzheimer's disease.2006Ingår i: Biological Psychiatry, ISSN 0006-3223, E-ISSN 1873-2402, Vol. 59, nr 2, s. 155-161Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: The hippocampal formation is damaged early in Alzheimer's disease (AD). An association between temporal lobe volume and cognitive function has been shown in several studies. Increased limbic-hypothalamic-pituitary-adrenal (LHPA) axis function has been suggested to be related to hippocampal atrophy and cognitive impairment. Our hypothesis was that there is a clear link between hippocampal volume -- notably of the CA1 region -- memory (episodic and visuospatial) and decreased feedback sensitivity in the LHPA axis in AD. METHODS: Sixteen medication-free outpatients with mild to moderate AD were included. Hippocampal volume was measured with magnetic resonance imaging. Dexamethasone suppression tests were performed using .5 mg and .25 mg dexamethasone. Three different components in the neuropsychological battery -- Rey 15 item memory test, Alzheimer's Disease Assessment Scale (ADAS) word recall and spatial span from Wechsler Adult Intelligence Scale - Revised neuropsychological instrument (WAIS-R NI) -- were found to represent episodic and visuospatial memory. RESULTS: Low hippocampal CA1 volume and high post-dexamethasone cortisol levels in combination were significantly associated with Rey 15 item memory and spatial span test outcomes. No association was found between LHPA feedback and hippocampal volume. CONCLUSIONS: Low hippocampal volume and a disturbed negative feedback in the LHPA axis link to specific cognitive impairments in Alzheimer's disease.

  • 14.
    Elgh, Eva
    et al.
    Umeå universitet, Medicinsk fakultet, Samhällsmedicin och rehabilitering, Geriatrik.
    Sundström, Torbjörn
    Umeå universitet, Medicinsk fakultet, Strålningsvetenskaper, Diagnostisk radiologi.
    Näsman, Birgitta
    Umeå universitet, Medicinsk fakultet, Samhällsmedicin och rehabilitering, Geriatrik.
    Riklund Åhlström, Katrine
    Umeå universitet, Medicinsk fakultet, Strålningsvetenskaper, Diagnostisk radiologi.
    Nyberg, Lars
    Umeå universitet, Samhällsvetenskaplig fakultet, Psykologi.
    Memory functions and rCBF (99m)Tc-HMPAO SPET: developing diagnostics in Alzheimer's disease2002Ingår i: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, E-ISSN 1619-7089, ISSN 1619-7070, Vol. 29, nr 9, s. 1140-1148Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Alzheimer's disease (AD) is a primary degenerative disease of the brain. The prevalence increases with age, with devastating consequences for the individual and society. The aim of this study was to evaluate whether patients with early AD show an altered regional cerebral blood flow (rCBF) compared with control persons. Furthermore, we aimed to investigate the correlation between rCBF in sublobar volumes of the brain and performance on memory tests. Memory tests were chosen to evaluate episodic and semantic memory. Fourteen patients (aged 75.2+/-8.8 years) with early AD and 15 control persons (aged 71.4+/-3.2 years) were included. rCBF measurements with single-photon emission tomography (SPET) using technetium-99m hexamethylpropylene amine oxime (HMPAO) were performed. The rCBF (99m)Tc-HMPAO SPET images were spatially transformed to fit a brain atlas and normalised for differences in rCBF (Computerised Brain Atlas software). Cortical and subcortical volumes of interest (VOIs) were analysed and compared. Compared with the controls, AD patients showed a significantly lower rCBF ratio in temporoparietal regions, including the left hippocampus. The diagnostic sensitivity and specificity for AD were high in temporoparietal regions. AD patients had significantly reduced performance on semantic and, in particular, episodic memory tests compared with age-matched normative data, and their performance on several episodic tests correlated with rCBF ratios in parietal and temporal regions, including the left hippocampus. The correlation between rCBF ratio and level of episodic memory performance suggests that abnormalities in rCBF pattern underlie impaired episodic memory functioning in AD.

  • 15.
    Lunde, Kristin Aaser
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Chung, Janete
    Dalen, Ingvild
    Pedersen, Kenn Freddy
    Linder, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Domellöf, Magdalena E.
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi. Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Elgh, Eva
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi.
    Macleod, Agnus D
    Tzoulis, Charalampos
    Larsen, Jan-Petter
    Tysnen, Ole-Bjørn
    Forsgren, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Counsell, Carl E.
    Alves, Guido
    Maple-Grødem, Jodi
    Association of glucocerebrosidase polymorphisms and mutations with dementia in incident Parkinson's disease2018Ingår i: Alzheimer's & Dementia, ISSN 1552-5260, E-ISSN 1552-5279, ISSN 1552-5260, Vol. 14, nr 10, s. 1293-1301Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Introduction

    Both polymorphisms and mutations in glucocerebrosidase (GBA) may influence the development of dementia in patients with Parkinson's disease.

    Methods

    Four hundred forty-two patients and 419 controls were followed for 7 years. Dementia was diagnosed using established criteria. Participants were analyzed for GBA genetic variants, including E326K, T369M, and L444P. Associations between GBA carrier status and dementia were assessed with Cox survival analysis.

    Results

    A total of 12.0% of patients with Parkinson's disease carried a GBA variant, and nearly half (22/53) of them progressed to dementia during follow-up. Carriers of deleterious GBA mutations (adjusted hazard ratio 3.81, 95% confidence interval 1.35 to 10.72; P = .011) or polymorphisms (adjusted hazard ratio 1.79; 95% confidence interval 1.07 to 3.00; P = .028) progressed to dementia more rapidly than noncarriers.

    Discussion

    GBA variants are of great clinical relevance for the development of dementia in Parkinson's disease, especially due to the relatively higher frequency of these alleles compared with other risk alleles.

  • 16. Marklund, Petter
    et al.
    Larsson, Anne
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Elgh, Eva
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Linder, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurologi.
    Riklund Åhlström, Katrine
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Forsgren, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurologi.
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi. Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Temporal dynamics of basal ganglia under-recruitment in Parkinson's disease: transient caudate abnormalities during updating of working memory.2009Ingår i: Brain, ISSN 0006-8950, E-ISSN 1460-2156, Vol. 132, nr Pt 2, s. 336-346Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Using hybrid-blocked/event-related fMRI and the 2-back task we aimed to decompose tonic and phasic temporal dynamics of basal ganglia response abnormalities in working memory associated with early untreated Parkinson's disease. In view of the tonic/phasic dopamine hypothesis, which posits a functional division between phasic D(2)-dependent striatal updating processes and tonic D(1)-dependent prefrontal context-maintenance processes, we predicted that newly diagnosed, drug-naïve Parkinson's disease patients, with selective striatal dopamine deprivation, would demonstrate transient rather than sustained activation changes in the basal ganglia during 2-back performance. Task-related activation patterns within discrete basal ganglia structures were directly compared between patients and healthy elderly controls. The obtained results yielded uniquely transient underactivation foci in caudate nuclei, putamen and globus pallidus in Parkinson's disease patients, which indicates suboptimal phasic implementation of striatal D(2)-dependent gating mechanisms during updating. Sustained underactivation was only seen in the anterior putamen, which may reflect initial signs of tonic control impairment. No significant changes were exhibited in prefrontal cortex. The present findings resonate well with the tonic/phasic dopamine account and suggest that basal ganglia under-recruitment associated with executive dysfunction in early Parkinson's disease might predominantly stem from deficiencies in phasic executive components subserved by striatum.

  • 17.
    Sjölie, Daniel
    et al.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för datavetenskap.
    Bodin, Kenneth
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för datavetenskap.
    Elgh, Eva
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Eriksson, Johan
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Janlert, Lars-Erik
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för datavetenskap.
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Effects of interactivity and 3D-motion on mental rotation brain activity in an immersive virtual environment2010Ingår i: Proceedings of the 28th international conference on Human factors in computing systems, Association for Computing Machinery (ACM), 2010, s. 869-878Konferensbidrag (Refereegranskat)
    Abstract [en]

    The combination of virtual reality (VR) and brain measurements is a promising development of HCI, but the maturation of this paradigm requires more knowledge about how brain activity is influenced by parameters of VR applications. To this end we investigate the influence of two prominent VR parameters, 3d-motion and interactivity, while brain activity is measured for a mental rotation task, using functional MRI (fMRI). A mental rotation network of brain areas is identified, matching previous results. The addition of interactivity increases the activation in core areas of this network, with more profound effects in frontal and preparatory motor areas. The increases from 3d-motion are restricted to primarily visual areas. We relate these effects to emerging theories of cognition and potential applications for brain-computer interfaces (BCIs). Our results demonstrate one way to provoke increased activity in task-relevant areas, making it easier to detect and use for adaptation and development of HCI.

  • 18.
    Stålnacke, Britt-Marie
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Rehabiliteringsmedicin.
    Elgh, Eva
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Sojka, Peter
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering.
    One-year follow-up of mild traumatic brain injury: cognition, disability and life satisfaction of patients seeking consultation.2007Ingår i: Journal of Rehabilitation Medicine, ISSN 1650-1977, E-ISSN 1651-2081, Vol. 39, nr 5, s. 405-11Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: To investigate cognitive function, symptoms, disabilities and life satisfaction of patients with mild traumatic brain injury who accepted consultation one year post-trauma. Design: Prospective study. Patients: Sixty-nine patients (16 accepted the consultation offered, 53 declined). Methods: At follow-up, the patients answered questionnaires about symptoms, disabilities (RHFUQ) and life satisfaction (LiSat-11). The patients who underwent consultation and their healthy control subjects were administered a neuropsychological evaluation. Results: In the group undergoing consultation, the number of cognitive tests with outcomes below cut-off limits (–1.5 SD) was statistically significantly higher compared with a control group (21 tests in 11 patients vs 8 tests in 7 control subjects; p = 0.025). The number of patients with one or more disability was statistically significantly higher among patients with consultation than without (94% and 34%, respectively; p < 0.001). Total RHFUQ score was statistically significantly higher for the group with consultation than without (5.9 ± 3.7 and 1.1 ± 2.3, respectively, p < 0.001). The group with consultation exhibited a lower level of life satisfaction (41.5 ± 10.4 vs 45.8 ± 13.8 for the non-consulting group; p = 0.057). Conclusion: The high frequency of occurrence of disabilities and lower cognitive functioning, together with the lower level of life satisfaction, appear to characterize patients choosing consultation 1 year post-injury. This highlights the importance of offering consultation for persons suffering mild head injuries.

  • 19.
    Sundström, Torbjörn
    et al.
    Umeå universitet, Medicinsk fakultet, Strålningsvetenskaper, Diagnostisk radiologi.
    Elgh, Eva
    Umeå universitet, Medicinsk fakultet, Samhällsmedicin och rehabilitering, Geriatrik.
    Larsson, Anne
    Umeå universitet, Medicinsk fakultet, Strålningsvetenskaper, Radiofysik.
    Näsman, Birgitta
    Umeå universitet, Medicinsk fakultet, Samhällsmedicin och rehabilitering, Geriatrik.
    Nyberg, Lars
    Umeå universitet, Samhällsvetenskaplig fakultet, Psykologi.
    Å Riklund, Katrine
    Umeå universitet, Medicinsk fakultet, Strålningsvetenskaper, Diagnostisk radiologi.
    Memory-provoked rCBF-SPECT as a diagnostic tool in Alzheimer's disease?2006Ingår i: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, E-ISSN 1619-7089, Vol. 33, nr 1, s. 73-80Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    PURPOSE: Alzheimer's disease (AD) is a primary degenerative disease that progressively affects all brain functions, with devastating consequences for the patient, the patient's family and society. Rest regional cerebral blood flow (rCBF) could have a strategic role in differentiating between AD patients and normal controls, but its use for this purpose has a low discriminatory capacity. The purpose of this study was to evaluate whether the diagnostic sensitivity of rCBF single-photon emission computed tomography (SPECT) could be increased by using an episodic memory task provocation, i.e. memory-provoked rCBF-SPECT (MP-SPECT). METHODS: Eighteen persons (73.2+/-4.8 years) with mild AD and 18 healthy elderly (69.4+/-3.9 years) were included in the study. The subjects were injected with (99m)Tc-hexamethylpropylene amine oxime (HMPAO) during memory provocation with faces and names, followed by an rCBF-SPECT study. The rCBF (99m)Tc-HMPAO SPECT images were analysed using statistical parametric mapping (SPM2). Peaks with a false discovery rate corrected value of 0.05 were considered significant. RESULTS: On MP-SPECT, the AD group showed a significant rCBF reduction in the left parietal cortex in comparison with healthy elderly. At rest, no significant group differences were seen. CONCLUSION: Memory provocation increased the sensitivity of rCBF-SPECT for the detection of AD-related blood flow changes in the brain at the group level. Further studies are needed to evaluate MP-SPECT as a diagnostic tool at the individual level. If a higher sensitivity for AD at the individual level is verified in future studies, a single MP-SPECT study might be sufficient in the clinical setting.

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