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  • 1.
    Dybjer, Elin
    et al.
    Department of Clinical Sciences, Lund University, Clinical Research Centre, Skane University Hospital, Malmö, Sweden.
    Nilsson, Peter M.
    Department of Clinical Sciences, Lund University, Clinical Research Centre, Skane University Hospital, Malmö, Sweden.
    Engstrom, Gunnar
    Department of Clinical Sciences, Lund University, Clinical Research Centre, Skane University Hospital, Malmö, Sweden.
    Helmer, Catherine
    University of Bordeaux, Inserm, Bordeaux Population Health Research Center, team LEHA, Bordeaux, France.
    Nägga, Katarina
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Acute Internal Medicine and Geriatrics. Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden.
    Pre-diabetes and diabetes are independently associated with adverse cognitive test results: a cross-sectional, population-based study2018In: BMC Endocrine Disorders, ISSN 1472-6823, E-ISSN 1472-6823, Vol. 18, article id 91Article in journal (Refereed)
    Abstract [en]

    Background

    Diabetes is a risk factor for cognitive impairment, but whether there is also a link between pre-diabetes and cognitive dysfunction is not yet fully established. The aim of this observational study was to investigate associations between pre-diabetes/diabetes and cognitive test results, and also between glucose levels measured during the Oral Glucose Tolerance Test (OGTT) and cognitive outcomes.

    Methods

    During 2007–2012, in all 2994 people (mean age 72 years), residing in Malmö, Sweden, underwent a clinical examination including the OGTT, cardiovascular measurements including carotid-femoral pulse wave velocity (c-f PWV) and two cognitive tests, the Mini Mental State Examination (MMSE), measuring global cognitive function, and A Quick Test of Cognitive Speed (AQT), measuring processing speed and executive functioning. Regression analyses were performed to investigate associations between: (a) categories of normal or impaired glucose metabolism, and (b) OGTT measurements, respectively, as exposure variables and cognitive test results as outcomes. Adjustments were made for demographics, lifestyle factors and cardiovascular risk factors.

    Results

    Participants with pre-diabetes and diabetes scored slightly worse cognitive test results compared to the control group. Results of participants with a long disease duration of diabetes since the baseline examination 13 years earlier were poorer (mean AQT test time 17.8 s slower than controls, p < 0.001). Linear associations were found between fasting and 2-h glucose and cognitive outcomes in the whole population, but also in a sub-analysis including only individuals without diabetes (for 2-h glucose and MMSE results: B = − 2.961, p = 0.005). Associations were stronger for older or less physically active individuals. When adjusting for cardiovascular risk factors, most correlations were non-significant.

    Conclusions

    Pre-diabetes and diabetes are associated with minor deficits in global cognitive function, processing speed and executive functioning. Long-standing diabetes is associated with bigger deficits. There appears to be a continuous inverse correlation between glucose levels and cognitive test results, also for people without diabetes. Associations are stronger in older and less physically active individuals. Cardiovascular factors are important mediating factors in the pathway between diabetes and cognitive dysfunction.

  • 2.
    Gustavsson, Anna-Märta
    et al.
    Lund University, Malmö, Sweden; Skåne University Hospital, Malmö, Sweden.
    van Westen, Danielle
    Lund University, Lund, Sweden.
    Stomrud, Erik
    Lund University, Malmö, Sweden; Skåne University Hospital, Malmö, Sweden.
    Engström, Gunnar
    Lund University, Malmö, Sweden.
    Nägga, Katarina
    Region Östergötland, Local Health Care Services in Central Östergötland, Department of Acute Internal Medicine and Geriatrics. Lund University, Malmö, Sweden.
    Hansson, Oskar
    Lund University, Malmö, Sweden; Skåne University Hospital, Malmö, Sweden.
    Midlife Atherosclerosis and Development of Alzheimer or Vascular Dementia2020In: Annals of Neurology, ISSN 0364-5134, E-ISSN 1531-8249, Vol. 87, no 1, p. 52-62Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To investigate whether midlife atherosclerosis is associated with different dementia subtypes and related underlying pathologies.

    METHODS: Participants comprised the cardiovascular cohort of the Swedish prospective population-based Malmö Diet and Cancer Study (N = 6,103). Carotid plaques and intima media thickness (IMT) were measured at baseline (1991-1994). Dementia incidence until 2014 was obtained from national registers. Diagnoses were reviewed and validated in medical records. In a cognitively unimpaired subcohort (n = 330), β-amyloid42 and tau were quantified in cerebrospinal fluid (CSF), and white matter hyperintensity volume, lacunar infarcts, and cerebral microbleeds were estimated on magnetic resonance imaging (2009-2015).

    RESULTS: During 20 years of follow-up, 462 individuals developed dementia (mean age at baseline = 57.5 ± 5.9 years, 58% women). Higher IMT in midlife was associated with an increased hazard ratio (HR) of all-cause dementia (adjusted HR = 1.14 [95% confidence interval (CI) = 1.03-1.26]) and vascular dementia (adjusted HR = 1.32 [95% CI = 1.10-1.57]) but not Alzheimer disease (AD) dementia (adjusted HR = 0.95 [95% CI = 0.77-1.17]). Carotid plaques were associated with vascular dementia when assessed as a 3-graded score (adjusted HR = 1.90 [95% CI = 1.07-3.38]). In the cognitively unimpaired subcohort (53.8 ± 4.6 years at baseline, 60% women), higher IMT in midlife was associated with development of small vessel disease (adjusted odds ratio [OR] = 1.47 [95% CI = 1.05-2.06]) but not significantly with abnormal CSF AD biomarkers (adjusted OR = 1.28 [95% CI = 0.87-1.90] for Aβ42 and 1.35 [95% CI = 0.86-2.13] for Aβ42 /p-tau). Carotid plaques revealed no significant association with any of the underlying brain pathologies.

    INTERPRETATION: Our findings support an association between midlife atherosclerosis and development of vascular dementia and cerebral small vessel disease but not between atherosclerosis and subsequent AD dementia or AD pathology. ANN NEUROL 2019.

  • 3.
    Hansson, Oskar
    et al.
    Lund University, Lund, Sweden; Skåne University Hospital, Lund, Sweden.
    Hall, Sara
    Lund University, Lund, Sweden; Skåne University Hospital, Lund, Sweden.
    Ohrfelt, Annika
    The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
    Zetterberg, Henrik
    The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
    Blennow, Kaj
    The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
    Minthon, Lennart
    Lund University, Lund, Sweden.
    Nägga, Katarina
    Lund University, Lund, Sweden.
    Londos, Elisabet
    Lund University, Lund, Sweden.
    Varghese, Shiji
    United Arab Emirates University, Al Ain, United Arab Emirates.
    Majbour, Nour K
    United Arab Emirates University, Al Ain, United Arab Emirates.
    Al-Hayani, Abdulmonem
    King Abdulaziz University, Jeddah, Saudi Arabia.
    El-Agnaf, Omar Ma
    United Arab Emirates University, Al Ain, United Arab Emirates; King Abdulaziz University, Jeddah, Saudi Arabia.
    Levels of cerebrospinal fluid α-synuclein oligomers are increased in Parkinson's disease with dementia and dementia with Lewy bodies compared to Alzheimer's disease2014In: Alzheimer's Research & Therapy, E-ISSN 1758-9193, Alzheimer's research & therapy, ISSN 1758-9193, Vol. 6, no 3, article id 25Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: The objective was to study whether α-synuclein oligomers are altered in the cerebrospinal fluid (CSF) of patients with dementia, including Parkinson disease with dementia (PDD), dementia with Lewy bodies (DLB), and Alzheimer disease (AD), compared with age-matched controls.

    METHODS: In total, 247 CSF samples were assessed in this study, including 71 patients with DLB, 30 patients with PDD, 48 patients with AD, and 98 healthy age-matched controls. Both total and oligomeric α-synuclein levels were evaluated by using well-established immunoassays.

    RESULTS: The levels of α-synuclein oligomers in the CSF were increased in patients with PDD compared with the controls (P < 0.05), but not in patients with DLB compared with controls. Interestingly, the levels of α-synuclein oligomers in the CSF were also significantly higher in patients with PDD (P < 0.01) and DLB (P < 0.05) compared with patients with AD. The levels of CSF α-synuclein oligomers and the ratio of oligomeric/total-α-synuclein could distinguish DLB or PDD patients from AD patients, with areas under the curves (AUCs) of 0.64 and 0.75, respectively. In addition, total-α-synuclein alone could distinguish DLB or PDD patients from AD patients, with an AUC of 0.80.

    CONCLUSIONS: The levels of α-synuclein oligomers were increased in the CSF from α-synucleinopathy patients with dementia compared with AD cases.

  • 4.
    Hansson, Oskar
    et al.
    Lund Univ, Sweden; Skane Univ Hosp, Sweden.
    Svensson, Martina
    Lund Univ, Sweden.
    Gustaysson, Anna-Marta
    Lund Univ, Sweden; Skane Univ Hosp, Sweden.
    Andersson, Emelie
    Lund Univ, Sweden.
    Yang, Yiyi
    Lund Univ, Sweden.
    Nägga, Katarina
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Acute Internal Medicine and Geriatrics. Lund Univ, Sweden.
    Hallmarker, Ulf
    Uppsala Univ, Sweden.
    James, Stefan
    Uppsala Univ, Sweden.
    Deierborg, Tomas
    Lund Univ, Sweden.
    Midlife physical activity is associated with lower incidence of vascular dementia but not Alzheimers disease2019In: Alzheimer's Research & Therapy, E-ISSN 1758-9193, ALZHEIMERS RESEARCH and THERAPY, Vol. 11, no 1, article id 87Article in journal (Refereed)
    Abstract [en]

    Background

    Physical activity might reduce the risk of developing dementia. However, it is still unclear whether the protective effect differs depending on the subtype of dementia. We aimed to investigate if midlife physical activity affects the development of vascular dementia (VaD) and Alzheimer’s disease (AD) differently in two large study populations with different designs.

    Methods

    Using a prospective observational design, we studied whether long-distance skiers of the Swedish Vasaloppet (n = 197,685) exhibited reduced incidence of VaD or AD compared to matched individuals from the general population (n = 197,684) during 21 years of follow-up (median 10, interquartile range (IQR) 5–15 years). Next, we studied the association between self-reported physical activity, stated twice 5 years apart, and incident VaD and AD in 20,639 participants in the Swedish population-based Malmo Diet and Cancer Study during 18 years of follow-up (median 15, IQR 14–17 years). Finally, we used a mouse model of AD and studied brain levels of amyloid-β, synaptic proteins, and cognitive function following 6 months of voluntary wheel running.

    Results

    Vasaloppet skiers (median age 36.0 years [IQR 29.0–46.0], 38% women) had lower incidence of all-cause dementia (adjusted hazard ratio (HR) 0.63, 95% CI 0.52–0.75) and VaD (adjusted HR 0.49, 95% CI 0.33–0.73), but not AD, compared to non-skiers. Further, faster skiers exhibited a reduced incidence of VaD (adjusted HR 0.38, 95% CI 0.16–0.95), but not AD or all-cause dementia compared to slower skiers. In the Malmo Diet and Cancer Study (median age 57.5 years [IQR 51.0–63.8], 60% women), higher physical activity was associated with reduced incidence of VaD (adjusted HR 0.65, 95% CI 0.49-0.87), but not AD nor all-cause dementia. These findings were also independent of APOE-ε4 genotype. In AD mice, voluntary running did not improve memory, amyloid-β, or synaptic proteins.

    Conclusions

    Our results indicate that physical activity in midlife is associated with lower incidence of VaD. Using three different study designs, we found no significant association between physical activity and subsequent development of AD.

  • 5.
    Hertze, Joakim
    et al.
    Lund University, Malmö, Sweden; Skåne University Hospital, Lund and Malmö, Sweden.
    Nägga, Katarina
    Lund University, Malmö, Sweden; Skåne University Hospital, Lund and Malmö, Sweden.
    Minthon, Lennart
    Lund University, Malmö, Sweden; Skåne University Hospital, Lund and Malmö, Sweden.
    Hansson, Oskar
    Lund University, Malmö, Sweden; Skåne University Hospital, Lund and Malmö, Sweden.
    Changes in cerebrospinal fluid and blood plasma levels of IGF-II and its binding proteins in Alzheimer's disease: an observational study2014In: BMC Neurology, ISSN 1471-2377, E-ISSN 1471-2377, Vol. 14, article id 64Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The Insulin-like Growth Factor (IGF)-related system is implicated in neuroregeneration and cell repair, as well as regulating lifespan. IGF-II, one component of this system, has also been found to affect memory functions in a rat model. In this study we explored changes in the IGF-related system in patients with Alzheimer's disease (AD), including changes in IGF-II levels.

    METHODS: We measured blood plasma and cerebrospinal fluid (CSF) levels of IGF-I, IGF-II, IGFBP-2 and IGFBP-3 in 72 healthy controls and 92 patients with AD.

    RESULTS: We found significantly lower blood plasma levels of IGF-II and IGFBP-3 in patients with AD, compared with controls. The levels of IGF-II and IGFBP-2 were significantly elevated in the CSF from patients with AD. We also found correlations between established CSF biomarkers for AD (tau and P-tau) and components of the IGF system.

    CONCLUSIONS: CSF and blood plasma levels of IGF-II and some of its binding proteins are changed in patients with AD. Further investigation into this area may unravel important clues to the nature of this disease.

  • 6.
    Jeppsson, Anna
    et al.
    Univ Gothenburg, Sweden.
    Wikkelso, Carsten
    Univ Gothenburg, Sweden.
    Blennow, Kaj
    Univ Gothenburg, Sweden; Sahlgrens Univ Hosp, Sweden.
    Zetterberg, Henrik
    Univ Gothenburg, Sweden; Sahlgrens Univ Hosp, Sweden; UCL Inst Neurol, England; UCL, England.
    Constantinescu, Radu
    Univ Gothenburg, Sweden.
    Remes, Anne M.
    Univ Oulu, Finland; Oulu Univ Hosp, Finland.
    Herukka, Sanna-Kaisa
    Kuopio Univ Hosp, Finland; Univ Eastern Finland, Finland.
    Rauramaa, Tuomas
    Univ Eastern Finland, Finland; Kuopio Univ Hosp, Finland.
    Nägga, Katarina
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Acute Internal Medicine and Geriatrics.
    Leinonen, Ville
    Oulu Univ Hosp, Finland; Univ Eastern Finland, Finland; Univ Oulu, Finland; Kuopio Univ Hosp, Finland.
    Tullberg, Mats
    Univ Gothenburg, Sweden.
    CSF biomarkers distinguish idiopathic normal pressure hydrocephalus from its mimics2019In: Journal of Neurology, Neurosurgery and Psychiatry, ISSN 0022-3050, E-ISSN 1468-330X, Vol. 90, no 10, p. 1117-1123Article in journal (Refereed)
    Abstract [en]

    Objective To examine the differential diagnostic significance of cerebrospinal fluid (CSF) biomarkers reflecting Alzheimers disease-related amyloid beta (A beta) production and aggregation, cortical neuronal damage, tau pathology, damage to long myelinated axons and astrocyte activation, which hypothetically separates patients with idiopathic normal pressure hydrocephalus (iNPH) from patients with other neurodegenerative disorders. Methods The study included lumbar CSF samples from 82 patients with iNPH, 75 with vascular dementia, 70 with Parkinsons disease, 34 with multiple system atrophy, 34 with progressive supranuclear palsy, 15 with corticobasal degeneration, 50 with Alzheimers disease, 19 with frontotemporal lobar degeneration and 54 healthy individuals (HIs). We analysed soluble amyloid precursor protein alpha (sAPP alpha) and beta (sAPP beta), A beta species (A beta 38, A beta 40 and A beta 42), total tau (T-tau), phosphorylated tau, neurofilament light and monocyte chemoattractant protein 1 (MCP-1). Results Patients with iNPH had lower concentrations of tau and APP-derived proteins in combination with elevated MCP-1 compared with HI and the non-iNPH disorders. T-tau, A beta 40 and MCP-1 together yielded an area under the curve of 0.86, differentiating iNPH from the other disorders. A prediction algorithm consisting of T-tau, A beta 40 and MCP-1 was designed as a diagnostic tool using CSF biomarkers. Conclusions The combination of the CSF biomarkers T-tau, A beta 40 and MCP-1 separates iNPH from cognitive and movement disorders with good diagnostic sensitivity and specificity. This may have important implications for diagnosis and clinical research on disease mechanisms for iNPH.

  • 7.
    Karlsson, Marit
    et al.
    Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Central County Primary Health Care.
    Milberg, Anna
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Social and Welfare Studies. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Geriatric and Hospital Based Homecare UHL.
    Nägga, Katarina
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Geriatrics. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine.
    Det är ju geriatrik som efterfrågas! "[Geriatrics are wanted!]."2002In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 99, no 40, p. 3976-3976Article in journal (Other (popular science, discussion, etc.))
    Abstract [en]

          

  • 8.
    Marcusson, Jan
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Geriatrics. Östergötlands Läns Landsting, MC - Medicincentrum, Geriatrik-LAH.
    Nägga, Katarina
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Geriatrics. Östergötlands Läns Landsting, MC - Medicincentrum, Geriatrik-LAH.
    No association between the a2-macroglobulin (A2M) deletion and Alzheimer's disease, and no change in A2M mRNA, protein, or protein expression2000In: Journal of neural transmission, ISSN 0300-9564, E-ISSN 1435-1463, Vol. 107, no 8-9, p. 1065-1079Article in journal (Refereed)
    Abstract [en]

    A polymorphism consisting of a deletion near the 5' splice site of exon 18 on the a2-macroglobulin (A2M) gene (A2M-2) has been suggested to be associated with Alzheimer's disease (AD) in family-based studies. We studied the A2M-2 allele together with the ApoE alleles in a large series on patients with AD (n = 449) and age-matched controls (n = 349). Neuropathologically confirmed diagnoses were available in 199 cases (94 AD and 107 control cases). We found no increase in A2M-2 genotype or allele frequencies in AD (27.5% and 14.6%) versus controls (26.4% and 14.9%). In contrast, a marked increase (p < 0.0001) in ApoE e4 genotype or allele frequencies was found in AD (66.6% and 41.2%) as compared with controls (29.8% and 16.5%), suggesting sufficient statistical power in our sample. No relation was found between the A2M-2 and the ApoE e4 allele. No change in A2M exon 17-18mRNA size or sequence or A2M protein size was found in cases carrying the A2M-2 deletion, suggesting that there is no biological consequences of the A2M intronic deletion. No change in A2M protein level in cerebrospinal fluid was found in AD, suggesting that the A2M-2 allele does not effect the A2M protein expression in the brain. The lack of an association between the A2M-2 allele and AD in the present study, and the lack of abnormalities in the A2M mRNA or protein suggest that the A2M-2 allele is not associated with AD.

  • 9.
    Nakanishi, Miharu
    et al.
    Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan.
    Endo, Kaori
    Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan.
    Hirooka, Kayo
    Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan.
    Nakashima, Taeko
    Rutgers University, The State University of New Jersey, Camden, NJ, USA.
    Morimoto, Yuko
    Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan.
    Granvik, Eva
    Lund University, Malmö, Sweden.
    Minthon, Lennart
    Lund University, Malmö, Sweden.
    Nägga, Katarina
    Lund University, Malmö, Sweden.
    Nishida, Atsushi
    Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan.
    Dementia behaviour management programme at home: impact of a palliative care approach on care managers and professional caregivers of home care services2018In: Aging & Mental Health, ISSN 1360-7863, E-ISSN 1364-6915, Vol. 22, no 8, p. 1063-1068Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: Care managers and professional caregivers of home care services are sometimes unaware of the psychosocial approaches to the challenging behaviour of dementia. Therefore, we developed a Behaviour Analytics & Support Enhancement (BASE) programme. We investigated the effects of the programme on the attitudes towards dementia care among professionals.

    METHOD: Forty-six participants in Japan received training in August 2016. The ongoing monitoring and assessment system was introduced to the participants for repeated measures of challenging behaviour. A 1-day follow-up meeting for debriefing was also performed after two months. A baseline and follow-up questionnaire survey was administered to the participating caregivers using a Japanese version of the Approaches to Dementia Questionnaire (ADQ) and the Zarit Burden Interview (ZBI).

    RESULTS: A significant improvement was observed in the total ADQ score among the participating caregivers from baseline to follow-up assessment. There was no significant difference between the baseline and follow-up assessment in the ZBI scores. In the follow-up meeting, several participants reported challenges and suggested solutions in facilitating a discussion on an action plan among professionals from various organizations.

    CONCLUSION: The implementation of the programme resulted in enhanced attitudes towards dementia care among the participants without an increased burden of care. Future studies should examine the programme's effectiveness on the challenging behaviour of persons with dementia.

  • 10.
    Nilsson, E D
    et al.
    Lund University, Skåne University Hospital, Malmö, Sweden.
    Elmståhl, S
    Lund University, Skåne University Hospital, Malmö, Sweden.
    Minthon, L
    Lund University, Skåne University Hospital, Malmö, Sweden.
    Nilsson, P M
    Lund University, Skåne University Hospital, Malmö, Sweden.
    Pihlsgård, M
    Lund University, Skåne University Hospital, Malmö, Sweden.
    Nägga, Katarina
    Lund University, Skåne University Hospital, Malmö, Sweden.
    Associations of central and brachial blood pressure with cognitive function: a population-based study2016In: Journal of Human Hypertension, ISSN 0950-9240, E-ISSN 1476-5527, Vol. 30, no 2, p. 95-99Article in journal (Refereed)
    Abstract [en]

    Previous observational studies on the association between brachial blood pressure (BP) and cognition have reported conflicting results. Central BP has been hypothesized to be more strongly related to cognition than brachial BP. The aim of this study was to assess the association between brachial as well as central BP and cognitive function, both cross-sectionally and with brachial BP measured 17 years before cognitive testing. The study population comprised 2548 individuals aged 61-85 years at follow-up (61.4% women). The cognitive tests administered were A Quick Test of cognitive speed and the Mini Mental State Examination. In fully adjusted linear regressions, small but significant cross-sectional associations were found between higher BP (systolic, diastolic and pulse pressure) and worse results on both of the cognitive tests (P-values <0.05). No significant prospective associations were found. Central BP did not show a stronger association than brachial BP did. After stratification, significant results were mainly found in the group taking BP-lowering drugs at follow-up. In summary, these findings add to existing evidence on the relationship between BP and cognition, but they do not support a superior role of central compared with brachial BP in the elderly.

  • 11.
    Nägga, Katarina
    Linköping University, Department of Neuroscience and Locomotion, Geriatrics. Linköping University, Faculty of Health Sciences.
    Aspects on clinical diagnosis of dementia, with focus on biological markers2004Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The clinical dementia diagnosis has become more complex with increasing knowledge of the heterogeneity of the disorder and its different aetiological aspects. A clinical dementia population and a control group were investigated with the following aims: I. To study the CSF levels of tau phosphorylated at threonine 181 (P-tau), total tau (T-tau) and ß-amyloid1-42 (Aß42) in the different diagnoses. II. To study associations between dementia disorder, cobalamin and/or folate deficiency, and gastritis. III. To study the presence and severity of CT brain changes in different dementia diagnoses. IV. To investigate to what extent different biomarkers and disease history contribute to the diagnostics of clinical dementia.

    I. CSF Levels of P-tau, T-tau and Aß42 were analysed with ELISA methods. Elevated CSF levels of P-tau were found in probable Alzheimer's disease (AD) patients compared with cognitively non-disturbed controls. Increased CSF T-tau, and decreased levels of Aß42 were found in both AD, mixed type of dementia, and vascular dementia (VaD) patients compared with the controls. Increased P-tau levels were more specific for AD pathology, but there was still an overlap with the controls, mixed dementia and VaD patients.

    II. Serological markers for cobalamin and folate deficiencies, and for gastritis were assessed in patients with different dementia diagnoses. Hyperhomocysteinaemia were commonly found in dementia without predominance in any of the investigated categories. Low levels of serum cobalamin or blood folate rarely reflected the elevated Hey levels. A lack of association between serological markers for cobalamin and folate deficiencies and for gastritis was demonstrated.

    III. A protocol for evaluation of the CT scans was used. Atrophy on the CT scans, although common in dementia, is an unspecific fmding in dementia of different backgrounds. White-matter changes and lacunes, indicating small-vessel disease, were common in dementia of different aetiologies. Dementia of mixed-type pathology was underestimated. More distinct criteria for this diagnostic category are warranted.

    IV. Partial Least Squares Discriminant Analysis (PLS-DA) was used on a large number of variables covering cognitive and biological markers and disease history. There were good discriminations of subgroups of dementia from the controls. However, the included variables were not able to distinguish between the investigated groups, indicating that several clinical parameters used in diagnosing dementia are in fact observed across different subtypes of dementia.

    It is concluded that there are no known biomarkers available that can provide a precise differential diagnosis of dementia. The clinical dementia diagnosis must still be based on a combination of a careful disease history, evaluation of risk factors, symptomatology, clinical findings, neurocognitive tests, blood analysis and other available methods such as CT and CSF markers.

  • 12.
    Nägga, Katarina
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Geriatric. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine in Linköping.
    Clinical and laboratory features and response to treatment in patients presenting with vitamin B-12 deficiency-related neurological syndromes - Invited comments: Neurol India. 2005 53(1):55-582005In: Neurology India, ISSN 0028-3886, E-ISSN 1998-4022, Vol. 53, no 1, p. 59-59p. 59-59Article in journal (Other academic)
    Abstract [en]

    Examines the clinical and laboratory features and response to treatment in patients presenting with vitamin B12 deficiency-related neurological syndromes. Effects of vitamin B12 deficiency on enzymatic pathways; Cnversion of homocysteine to methionine and the conversion of methylmalonyl coenzyme A to succinyl coenzyme A; Methylation reactions involving homocysteine metabolism in the nervous system.

  • 13.
    Nägga, Katarina
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Geriatrics. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine.
    Klinisk demensdiagnostik2005In: Incitament, ISSN 1103-503X, Vol. 1, p. 75-78Article in journal (Other (popular science, discussion, etc.))
  • 14.
    Nägga, Katarina
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Geriatrics. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine.
    Vitamin B12 and folate--a question of balance?2005In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 102, p. 2975-2975Article in journal (Other academic)
  • 15.
    Nägga, Katarina
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Geriatrics. Östergötlands Läns Landsting, MC - Medicincentrum, Geriatrik-LAH.
    Bogdanovic, N.
    Marcusson, Jan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Geriatrics. Östergötlands Läns Landsting, MC - Medicincentrum, Geriatrik-LAH.
    Gaba transporters (GAT-1) in Alzheimer´s disease.1999In: Journal of neural transmission, ISSN 0300-9564, E-ISSN 1435-1463, Vol. 106, no 11-12, p. 1141-1149Article in journal (Refereed)
    Abstract [en]

    The presynaptically located gamma-aminobutyric acid (GABA) transporter (GAT-1) was studied in a group of patients with Alzheimer's disease (AD) and in a control group using the GAT-1 selective radioligand [H-3]tiagabine. Post mortem brain tissue from frontal cortex, temporal cortex, and caudate nucleus from 18 AD patients and 23 age-matched controls were studied. The binding was saturable (Kd 26 nM) and region specific. There were no significant differences between the groups with respect to the binding capacity (Bmax) and binding affinity (Kd). The unaltered [H-3]tiagabine binding to GAT-1 protein indicates that intrinsic GABA neurons are spared in Alzheimer's disease.

  • 16.
    Nägga, Katarina
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Geriatric. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine in Linköping.
    Dong, Huan-Ji
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Marcusson, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Geriatric. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine in Linköping.
    Olin Skoglund, Sabina
    Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine in Linköping.
    Wressle, Ewa
    Linköping University, Department of Clinical and Experimental Medicine, Geriatric. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine in Linköping.
    Health-related factors associated with hospitalization for old people: Comparisons of elderly aged 85 in a population cohort study2012In: Archives of gerontology and geriatrics (Print), ISSN 0167-4943, E-ISSN 1872-6976, Vol. 54, no 2, p. 391-397Article in journal (Refereed)
    Abstract [en]

    The aim of this population-based study was to (1) describe living conditions and actual health care utilization among 85 year olds; (2) determine factors that affect hospital admissions in this age. The study was conducted on 85-year-old residents in Linkoping municipality, Sweden. The data collected included medical records, health care utilization during the preceding 12 months and a postal questionnaire on assistance, assistive technology, functional impairment, feelings of loneliness, worries and health-related quality of life measured by the EQ-5D. Out of 650 eligible individuals, 496 (78% of those alive) participated. Despite the prevalence of multi-morbidity (68%) and mental discomfort, the majority managed self-care (85%), usual activities (74%) and had high (andgt;60/100) self-rated health evaluated by a visual analog scale (VAS). The non-hospitalized group reported a better health status than the hospitalized group in terms of medical aspects, living conditions and subjective estimation. Factors associated with in-patient care were an increased number of general practitioner visits, more assistive technology, community assistance, multimorbidity and/or diagnosed congestive heart failure and arrhythmia.

  • 17.
    Nägga, Katarina
    et al.
    Linköping University, Department of Neuroscience and Locomotion, Geriatrics. Linköping University, Faculty of Health Sciences.
    Garcia-Colque, Jorge
    Linköping University, Department of Neuroscience and Locomotion, Geriatrics. Linköping University, Faculty of Health Sciences.
    Zetterberg, Henrik
    Department of Clinical Neuroscience, Section of Experimental Neuroscience, University of Göteborg, Sahlgrenska University Hospital, Mölndal.
    Blennow, Kaj
    Department of Clinical Neuroscience, Section of Experimental Neuroscience, University of Göteborg, Sahlgrenska University Hospital, Mölndal and The Medical Research Council, AstraZeneca R&D, Mölndal.
    Gottfries, Johan
    Medicinal Chemistry, AstraZeneca R&D, Mölndal, Sweden.
    Marcusson, Jan
    Linköping University, Department of Neuroscience and Locomotion, Geriatrics. Linköping University, Faculty of Health Sciences.
    Evaluation of factors of importance for clinical dementia diagnosis2005In: Dementia and Geriatric Cognitive Disorders, ISSN 1420-8008, E-ISSN 1421-9824, Vol. 19, no 5-6, p. 289-298Article in journal (Refereed)
    Abstract [en]

    Diagnosing clinical dementia is based on an assessment of different variables, such as the patient’s medical history, known risk factors, and biochemical features. Partial least squares discriminant analysis was used to evaluate variables of importance for diagnosing dementia in a clinical dementia population. Polymorphism for genotypes of glutathione S-transferase (GST) and sulfotransferase 1A1, hypothetically of importance in dementia disorders, was also included in the analysis. The study population consisted of 73 patients with Alzheimer’s disease (AD), 14 with mixed dementia, 75 patients with vascular dementia, and 28 control cases. We found that several of the variables, such as the presence of ApoE4 allele, high cerebrospinal fluid levels of total tau protein, low levels of β-amyloid(1–42), and a low score on the Mini-Mental State Examination, facilitated a discrimination between the diagnoses compared with the controls. The different diagnoses overlapped. There were indications that genotypes of GSTs contributed to a subgrouping within AD.

  • 18.
    Nägga, Katarina
    et al.
    Linköping University, Department of Neuroscience and Locomotion, Geriatrics. Linköping University, Faculty of Health Sciences.
    Gottfries, J.
    Medicinal Chemistry, AstraZeneca R and D, Mölndal, Sweden.
    Blennow, K.
    Department of Clinical Neuroscience, University of Göteborg, Sahlgrenska University Hospital, Mölndal, Sweden.
    Marcusson, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Geriatric. Linköping University, Faculty of Health Sciences.
    Cerebrospinal fluid phospho-tau, total tau and β-amyloid1-42 in the differentiation between Alzheimer's disease and vascular dementia2002In: Dementia and Geriatric Cognitive Disorders, ISSN 1420-8008, E-ISSN 1421-9824, Vol. 14, no 3-4, p. 183-190Article in journal (Refereed)
    Abstract [en]

    The two most frequently examined biomarkers in the diagnosis of dementia are cerebrospinal fluid (CSF) tau and β-amyloid1-42 (Aβ1-42). An assay for tau phosphorylated at threonine 181 (phospho-tau) has recently been developed. We studied these three markers in patients with possible Alzheimer's disease (AD; n = 23), probable AD (n = 50), AD with relevant cerebrovascular disease (AD with CVD; n = 14), possible vascular dementia (VaD; n = 39), probable VaD (n = 36), cognitively impaired (n = 13) and 27 neurologically healthy controls. Compared with the controls, tau levels were significantly increased in possible AD, probable AD, AD with CVD and probable VaD. Aβ1-42 was decreased in all dementia groups compared with the controls. In contrast, phospho-tau levels were increased only in probable AD compared with the controls. From the results of the present study, it is concluded that neither measurement of phospho-tau, tau nor Aβ1-42 in CSF can discriminate entirely between dementia and cognitively non-disturbed controls or between dementia of different aetiologies in the clinical diagnostic procedure.

  • 19.
    Nägga, Katarina
    et al.
    Lund University, Malmö, Sweden.
    Hansson, Oskar
    Lund University, Malmö, Sweden.
    van Westen, Danielle
    Lund University, Malmö, Sweden; Skåne University Health Care Lund, Lund, Sweden.
    Minthon, Lennart
    Lund University, Malmö, Sweden.
    Wennström, Malin
    Lund University, Malmö, Sweden.
    Increased levels of hyaluronic acid in cerebrospinal fluid in patients with vascular dementia2014In: Journal of Alzheimer's Disease, ISSN 1387-2877, E-ISSN 1875-8908, Vol. 42, no 4, p. 1435-1441Article in journal (Refereed)
    Abstract [en]

    Hyaluronic acid (HA) has been shown to affect angiogenesis and the function of the blood-brain barrier, and a crucial role for HA in atherosclerosis has been described. We have recently demonstrated changes in the levels of HA in cerebrospinal fluid (CSF) in patients with Alzheimer's disease (AD) with documented vascular alterations. To further investigate if the level of HA in CSF can be used as a clinical diagnostic biomarker to identify vascular pathology in dementia, we analyzed the levels of HA in the CSF of patients with vascular dementia (VaD) (n = 46), AD (n = 45), and controls without dementia (n = 26). In line with our previous data, we found significantly increased levels of HA in CSF from patients with VaD compared with controls, whereas the levels of HA in patients with AD were found to be unaltered compared with controls and patients with VaD. We also detected increased levels of HA in individuals with vascular changes determined as significant white matter changes or previous infarction on cranial computed tomography or magnetic resonance imaging, compared with individuals without these findings. Furthermore, we found a significant positive correlation between the levels of HA and the CSF/serum albumin ratio, an indicator of blood-brain barrier integrity, in patients with VaD and AD, supporting the role of HA in vascular changes in the brain. Our results indicate a potential diagnostic value for the detection of vascular brain changes in dementia using CSF levels of HA, but emphasize the importance of further development of more sensitive HA assays.

  • 20.
    Nägga, Katarina
    et al.
    Linköping University, Department of Neuroscience and Locomotion, Geriatrics. Linköping University, Faculty of Medicine and Health Sciences.
    Marcusson, Jan
    Linköping University, Department of Neuroscience and Locomotion, Geriatrics. Linköping University, Faculty of Medicine and Health Sciences.
    Associated physical disease in a demented population1998In: Aging (Milan, Italy), ISSN 0394-9532, Vol. 10, no 6, p. 440-4Article in journal (Refereed)
    Abstract [en]

    Clinical experience indicates that physical diseases are probably underdiagnosed in patients suffering from dementia. We investigated the prevalence of physical diseases in patients with different types of dementia by means of a retrospective patient record survey including 236 inpatients and outpatients referred for dementia evaluation to the Dementia Investigation Unit, University Hospital in Linköping during 1994. Forty-four patients had dementia of the Alzheimer type, 78 had vascular dementia, 28 had dementia due to multiple etiologies, 42 were not demented, and 44 patients could not be classified by the DSM IV criteria. The physical diseases were registered as separate diagnoses comprising all newly-diagnosed physical diseases and previously known diseases that had exacerbated and contributed to the medical contact. Sixty-four percent of the patients had previously unknown physical diseases and/or exacerbation of previously known diseases. The most common physical conditions were cobalamin deficiency and infectious diseases, which occurred in 27% and 24% of the patients, respectively. There was no difference in the number or kinds of diagnoses between the diagnostic groups. Associated physical diseases were underdiagnosed in patients referred for dementia evaluation. We suggest that thorough medical investigation and adequate treatment are of importance in the management of dementia.

  • 21.
    Nägga, Katarina
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Geriatric . Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine.
    Marcusson, Jan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Geriatric . Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine.
    Effects of cobalamin supplementation - A study on dementia patients with cobalamin deficiency2002In: Neurobiology of Aging, ISSN 0197-4580, E-ISSN 1558-1497, Vol. 23, no 1, p. 427-Conference paper (Other academic)
  • 22.
    Nägga, Katarina
    et al.
    Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine in Linköping. Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Clinical Memory Research Unit Lund University.
    Mayer, Sibylle
    Cinical Memory Research Unit Lund University.
    Marcusson, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine in Linköping.
    Wressle, Ewa
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine in Linköping.
    Evaluation of short cognitive screening tests in 85-year-old men and women2015In: European Geriatric Medicine, ISSN 1878-7649, E-ISSN 1878-7657, Vol. 6, no 6, p. 545-550Article in journal (Refereed)
    Abstract [en]

    Introduction: The study aimed to investigate different aspects of cognition using the Cognitive Assessment Battery (CAB) in community-dwelling older adults aged 85 years. We also investigated the eventual influence of sex on the results and aimed to identify predictors for further cognitive decline after 1 year. Methods: CAB consists of 10 subtests covering the cognitive domains of speed and attention, learning and episodic memory, visuospatial abilities, language, and executive functions. Cognitive tests were performed at baseline (n = 335) and follow-up after 1 year (n = 270). Results: Univariate statistics revealed that men performed better than women on episodic memory (P < 0.05) and on the naming test (P < 0.001). However, floor effects in the paragraph memory test were revealed. There was a high rate of abnormal results on Token Test (67%), PaSMO (50%), Clox (48%), and the cube copying (40%) tests in participants with normal cognition. Logistic regression showed that impaired results on the Stroop III test (odds ratio, 2.38; P < 0.05) was independently associated with an increased risk of cognitive decline. Conclusion: Men performed better than women on the memory and on the naming test. However, due to floor effects in the paragraph memory test in 85 year olds, these results can be disputed. The high rate of abnormal results on the Token Test, PaSMO, Clox, and the cube copying tests in cases with normal cognition indicate that these tests are less suitable for screening in the age group. Impaired result on the Stroop test increased the risk more than two-fold for cognitive decline after 1 year.

  • 23.
    Nägga, Katarina
    et al.
    Linköping University, Department of Neuroscience and Locomotion, Geriatrics. Linköping University, Faculty of Health Sciences.
    Rajani, Rupesh
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Mårdh, Erik
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Borch, Kurt
    Linköping University, Department of Biomedicine and Surgery, Surgery. Linköping University, Faculty of Health Sciences.
    Mårdh, Sven
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Marcusson, Jan
    Linköping University, Department of Neuroscience and Locomotion, Geriatrics. Linköping University, Faculty of Health Sciences.
    Cobalamin, folate, methylmalonic acid, homocysteine, and gastritis markers in dementia2003In: Dementia and Geriatric Cognitive Disorders, ISSN 1420-8008, E-ISSN 1421-9824, Vol. 16, no 4, p. 269-275Article in journal (Refereed)
    Abstract [en]

    The prevalence of dementia disorders, cobalamin and/or folate deficiency as well as gastritis increases with age. To investigate whether there is an association between these conditions, plasma homocysteine (Hcy), serum methylmalonic acid, serum cobalamin and blood folate concentrations were measured. Gastritis was indirectly diagnosed by measuring serum antibodies against H,K-ATPase, Helicobacter pylori and intrinsic factor, using enzyme-linked immunosorbent assays. The studied groups consisted of 47 patients with Alzheimer’s disease (AD), 9 with AD pathology in combination with additive vascular lesions, 59 with vascular dementia, 8 who were cognitively impaired, and 101 control cases. Plasma Hcy concentrations were significantly elevated in the dementia groups, with the highest levels in patients with vascular pathology. We conclude that hyperhomocysteinemia is a common finding in patients with dementia disorders of different etiologies. The markers for gastritis did not contribute to an elucidation of a possible connection between this condition, dementia disorders, or cobalamin/folate deficiency.

  • 24.
    Nägga, Katarina
    et al.
    Linköping University, Department of Neuroscience and Locomotion, Geriatrics. Linköping University, Faculty of Health Sciences.
    Rådberg, Claes
    Linköping University, Department of Medicine and Care, Radiology. Linköping University, Faculty of Health Sciences.
    Marcusson, Jan
    Linköping University, Department of Neuroscience and Locomotion, Geriatrics. Linköping University, Faculty of Health Sciences.
    CT brain findings in clinical dementia investigation: underestimation of mixed dementia2004In: Dementia and Geriatric Cognitive Disorders, ISSN 1420-8008, E-ISSN 1421-9824, Vol. 18, no 1, p. 59-66Article in journal (Refereed)
    Abstract [en]

    Dementia has been found to display a more heterogeneous clinical picture than previously recognized. We investigated brain changes on computed tomography (CT) in a clinical dementia population consisting of 67 cases with Alzheimer's disease (AD), 13 with mixed dementia (AD and vascular dementia, VaD), 71 with VaD, and 12 cases that were not demented. Temporal cortical atrophy and atrophy around the temporal horns were more common in patients with mixed dementia compared to patients with VaD and the non-demented, respectively. Frontal white matter changes were present in 64% of AD, in 85% of mixed dementia and in 79% of VaD cases, but there were no differences between the dementia groups. Lacunes were present in almost 40% of AD cases and in 80 and 85% of VaD and mixed dementia cases, respectively. Only 14% of the VaD cases had large infarcts on the CT. We conclude that large infarcts were rare, even in VaD cases. The increased incidence of white matter changes and lacunes in AD patients strongly indicates an underestimation of the mixed dementia diagnosis. More distinct criteria for this diagnostic category are warranted.

  • 25.
    Prince, J.A.
    et al.
    Center for Genomics Research, Karolinska Institute, Stockholm, Sweden.
    Feuk, L.
    Center for Genomics Research, Karolinska Institute, Stockholm, Sweden.
    Sawyer, S.L.
    Center for Genomics Research, Karolinska Institute, Stockholm, Sweden.
    Gottfries, J.
    Department of Medicinal Chemistry, AstraZeneca, Mölndal, Sweden.
    Ricksten, A.
    Department of Clinical Neuroscience and Transfusion Medicine, University of Göteborg, Sahlgren's University Hospital, Sweden.
    Nägga, Katarina
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Geriatric . Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine.
    Bogdanovic, N.
    Department of Clinical Neuroscience and Family Medicine, Karolinska Institute, Huddinge University Hospital, Stockholm, Sweden.
    Blennow, K.
    Department of Clinical Neuroscience and Transfusion Medicine, University of Göteborg, Sahlgren's University Hospital, Sweden.
    Brookes, A.J.
    Center for Genomics Research, Karolinska Institute, Stockholm, Sweden.
    Lack of replication of association findings in complex disease: An analysis of 15 polymorphisms in prior candidate genes for sporadic Alzheimer's disease2001In: European Journal of Human Genetics, ISSN 1018-4813, E-ISSN 1476-5438, Vol. 9, no 6, p. 437-444Article in journal (Refereed)
    Abstract [en]

    There is considerable enthusiasm for the prospect of using common polymorphisms (primarily single nucleotide polymorphisms, SNPs) in candidate genes to unravel the genetics of complex disease. This approach has generated a number of findings of loci which are significantly associated with sporadic Alzheimer's disease (AD). In the present study, a total of 15 genes of interest were chosen from among the previously published reports of significant association in AD. Genotyping was performed on polymorphisms within those genes (14 SNPs and one deletion) using Dynamic Allele Specific Hybridization (DASH) in 204 Swedish patients with sporadic late-onset AD and 186 Swedish control subjects. The genes chosen for analysis were, low-density lipoprotein receptor-related protein (LRP1), angiotensin converting enzyme (DCP1), alpha-2-macroglobulin (A2M), bleomycin hydrolase (BLMH), dihydrolipoyl S-succinyltransferase (DLST), tumour necrosis factor receptor superfamily member 6 (TNFRSF6), nitric oxide synthase (NOS3), presenilin 1 (PSEN1), presenilin 2 (PSEN2), butyrylcholinesterase (BCHE), Fe65 (APBB1), oestrogen receptor alpha (ESR1), cathepsin D (CTSD), methylenetetrahydrofolate reductase (MTHFR), and interleukin 1A (IL1A). We found no strong evidence of association for any of these loci with AD in this population. While the possibility exists that the genes analysed are involved in AD (ie they have weak effects and/or are population specific), results reinforce the need for extensive replication studies if we are to be successful in defining true risk factors in complex diseases.

  • 26.
    Redéen, Stefan
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Surgery . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Ryberg, Anna
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Petersson, Fredrik
    Ryhov Hospital.
    Eriksson, Olle
    Linköping University, Department of Computer and Information Science, Statistics. Linköping University, Faculty of Arts and Sciences.
    Nägga, Katarina
    Linköping University, Department of Neuroscience and Locomotion, Geriatrics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine.
    Borch, Kurt
    Linköping University, Department of Clinical and Experimental Medicine, Surgery . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Homocysteine Levels in Chronic Gastritis and Other Conditions: Relations to Incident Cardiovascular Disease and Dementia2010In: DIGESTIVE DISEASES AND SCIENCES, ISSN 0163-2116, Vol. 55, no 2, p. 351-358Article in journal (Refereed)
    Abstract [en]

    Background Homocysteine levels in circulation are determined by several factors and hyperhomocysteinemia is reportedly associated with cardiovascular diseases and dementia. The aim of this study is to determine the relation of chronic gastritis and other conditions to homocysteine levels and their relation to incident cardiovascular diseases and dementia. Methods An adult population-based cohort (N = 488) was screened for H. pylori infection, gastro-duodenitis ( endoscopic biopsies), disease history, and lifestyle factors. Blood samples were analyzed for pepsinogen I and II ( gastric function), vitamin B12, folate, homocysteine, and cystatin C ( renal function). The methylenetetrahydrofolate reductase C677T polymorphism reportedly associated with hyperhomocysteinemia was analyzed by pyrosequencing. Incident cardiovascular diseases and dementia were monitored during a median follow-up interval of 10 years. Results At baseline, there was a positive relation of S-homocysteine to male gender, age, S-cystatin C, methylenetetrahydrofolate reductase 677TT genotype and atrophic gastritis. During follow-up, cardiovascular diseases occurred in 101/438 and dementia in 25/488 participants, respectively. Logistic regression analysis ( adjusting for gender, age at baseline, follow-up interval, BMI, smoking, alcohol consumption, NSAID use, P-cholesterol, and P-triglycerides) showed an association of S-homocysteine higher than 14.5 mu mol/l to cardiovascular diseases (OR 2.05 [95% c.i. 1.14-3.70]), but not to dementia overall. Conclusions Gender, age, vitamin B12, folate, renal function, atrophic gastritis and the methylenetetrahydrofolate 677TT genotype were significant determinants of homocysteine levels, which were positively related to incident cardiovascular diseases.

  • 27.
    Rådholm, Karin
    et al.
    Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Primary Health Care in Central County. Linköping University, Department of Medical and Health Sciences, General Practice. Linköping University, Faculty of Health Sciences.
    Östgren, Carl Johan
    Linköping University, Department of Medical and Health Sciences, General Practice. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in West Östergötland, Primary Health Care in Motala.
    Alehagen, Urban
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Cardiology in Linköping.
    Falk, Magnus
    Linköping University, Department of Medical and Health Sciences, General Practice. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Primary Health Care in Central County. Östergötlands Läns Landsting, Local Health Care Services in West Östergötland, Research & Development Unit in Local Health Care.
    Wressle, Eva
    Linköping University, Department of Clinical and Experimental Medicine, Geriatric. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine in Linköping.
    Marcusson, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Geriatric. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine in Linköping.
    Nägga, Katarina
    Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine in Linköping. Linköping University, Department of Clinical and Experimental Medicine, Geriatric. Linköping University, Faculty of Health Sciences.
    Atrial fibrillation (AF) and co-morbidity in elderly. A population based survey of 85 years old subjects.2011In: Archives of gerontology and geriatrics (Print), ISSN 0167-4943, E-ISSN 1872-6976, Vol. 52, no 3, p. e170-e175Article in journal (Refereed)
    Abstract [en]

    The occurrence of AF increases sharply with age. The aim of this study was to explore and compare prevalent co-morbidity and self-estimated health-related quality of life (HRQoL) in subjects with AF versus subjects with sinus rhythm or pacemaker in 85 years old subjects. We analyzed data from a population of 336 eighty-five years old subjects participating in the Elderly in Linköping Screening Assessment (ELSA-85) study. Medical history was obtained from postal questionnaire, medical records and during medical examination that included a physical examination, cognitive tests, non-fasting venous blood samples and electrocardiographic (ECG) examination. 19% had an ECG showing AF. There were very few significant differences regarding medical history, self-estimated quality of life (QoL), laboratory- and examination findings and use of public health care between the AF group and the non-AF group. The study showed that the population of 85 years old subjects with AF was surprisingly healthy in terms of prevalent co-existing medical conditions, healthcare contacts and overall HRQoL. We conclude that elderly patients with AF do not in general have increased co-morbidity than subjects without AF.

  • 28.
    Schultz, Nina
    et al.
    Lund Univ, Sweden.
    Janelidze, Shorena
    Lund Univ, Sweden.
    Byman, Elin
    Lund Univ, Sweden.
    Minthon, Lennart
    Lund Univ, Sweden.
    Nägga, Katarina
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Acute Internal Medicine and Geriatrics. Lund Univ, Sweden.
    Hansson, Oskar
    Lund Univ, Sweden; Skane Univ Hosp, Sweden.
    Wennstrom, Malin
    Lund Univ, Sweden.
    Levels of islet amyloid polypeptide in cerebrospinal fluid and plasma from patients with Alzheimers disease2019In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 14, no 6, article id e0218561Article in journal (Refereed)
    Abstract [en]

    The biologically active pancreatic hormone peptide islet amyloid polypeptide (IAPP) regulates brain functions such as appetite and cognition. It also plays a role in clearance of amyloid beta (A beta), a peptide implicated in the dementia disorder Alzheimers disease (AD). If IAPP becomes modified, it loses its biological activity and starts to aggregate. Such aggregations have been found in the AD brain and decreased plasma levels of the unmodified IAPP (uIAPP) have been shown in the same patients. In the current study, we analyze levels of uIAPP and total IAPP (unmodified and modified) in cerebrospinal fluid (CSF) to investigate its potential as a biomarker for AD. We found no differences in neither CSF nor plasma levels of uIAPP or total IAPP in AD patients compared to cognitive healthy individuals (NC). The levels of uIAPP in CSF of NC were positively correlated with uIAPP in plasma, Q-albumin and albumin levels in CSF, but negatively correlated with CSF levels of t-tau and p-tau. These findings were not seen in AD patients. Levels of total CSF IAPP correlated positively with total Q-albumin and albumin levels in CSF in both AD and NC. In addition, total plasma IAPP correlated positively with CSF t-tau and p-tau in NC and negatively with CSF A beta(42) in AD patients. To conclude, our studies did not find evidence supporting the use of CSF IAPP as an AD biomarker. However, our findings, indicating a compromised translocation of uIAPP in and out of the brain in AD patients as well as the correlations between total plasma IAPP and AD biomarkers, encourage further research on the role for IAPP in AD.

  • 29.
    Schwertner, Emilia
    et al.
    Center for Alzheimer Research, Division of Clinical Geriatrics, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Huddinge, Sweden.
    Secnik, Juraj
    Center for Alzheimer Research, Division of Clinical Geriatrics, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Huddinge, Sweden.
    Garcia-Ptacek, Sara
    Center for Alzheimer Research, Division of Clinical Geriatrics, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Huddinge, Sweden; Department of Internal Medicine, Section for Neurology, Södersjukhuset, Stockholm, Sweden.
    Johansson, Bjorn
    Department of Molecular Medicine and Surgery Stockholm, Karolinska Institutet, Sweden; Theme Aging, Karolinska University Hospital, Huddinge, Sweden.
    Nägga, Katarina
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Acute Internal Medicine and Geriatrics. Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden.
    Eriksdotter, Maria
    Center for Alzheimer Research, Division of Clinical Geriatrics, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Huddinge, Sweden; Theme Aging, Karolinska University Hospital, Huddinge, Sweden.
    Winblad, Bengt
    Theme Aging, Karolinska University Hospital, Huddinge, Sweden; Center for Alzheimer Research, Division of Neurogeriatrics, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Huddinge, Sweden.
    Religa, Dorota
    Center for Alzheimer Research, Division of Clinical Geriatrics, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Huddinge, Sweden; Theme Aging, Karolinska University Hospital, Huddinge, Sweden.
    Antipsychotic Treatment Associated With Increased Mortality Risk in Patients With Dementia. A Registry-Based Observational Cohort Study2019In: Journal of the American Medical Directors Association, ISSN 1525-8610, E-ISSN 1538-9375, Vol. 20, no 3, p. 323-329.e2Article in journal (Refereed)
    Abstract [en]

    Objective

    To assess all-cause mortality patients with dementia treated with typical and atypical antipsychotic drugs (APDs).

    Design

    Registry-based cohort study.

    Setting and participants

    A total of 58,412 patients diagnosed with dementia and registered in the Swedish Dementia Registry were included in the study. Of the study sample, 2526 of the patients were prescribed APDs. Of these, 602 patients were prescribed typical APDs and 1833 patients were prescribed atypical APDs. Ninety-one patients were prescribed both typical and atypical APDs.

    Measurements

    All-cause mortality based on Swedish Cause of Death Register. Adjusted hazard ratios of mortality were calculated according to class of APDs (typical or atypical) prescribed. Final models were adjusted for age at dementia diagnosis, sex, Charlson comorbidity index, living arrangement, and Mini-Mental State Examination.

    Results

    In the adjusted models, use of APDs at the time of dementia diagnosis was associated with increased mortality risk in the total cohort (hazard ratio = 1.4; 95% confidence interval 1.3–1.5). After stratifying for dementia types, increased mortality risks associated with APDs were found in patients with Alzheimer's disease, mixed dementia, unspecified dementia, and vascular dementia. Higher risk for mortality was found with typical APDs in patients with mixed and vascular dementia and with atypical APDs in patients with Alzheimer's disease, mixed, unspecified, and vascular dementia. Furthermore, in patients with Alzheimer's disease who had typical APDs, use lower risk of death emerged in comparison with patients with atypical APDs.

    Conclusions/Implications

    Both the use of atypical and typical APDs increased the risk of death in patients with dementia even after adjusting for differences in basic characteristics between groups. Although we cannot rule out the influence of residual confounding, these results would seem to add to studies suggesting caution in APD prescription for patients with dementia.

    The full text will be freely available from 2020-02-27 15:14
  • 30. Sjögren, M
    et al.
    Vanderstichele, H
    Ågren, H
    Zachrisson, O
    Edbagge, M
    Wikkelso, C
    Skoog, I
    Wallin, A
    Wahlund, LO
    Marcusson, Jan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Geriatrics. Östergötlands Läns Landsting, MC - Medicincentrum, Geriatrik-LAH.
    Nägga, Katarina
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Geriatrics. Östergötlands Läns Landsting, MC - Medicincentrum, Geriatrik-LAH.
    Andreasen, N
    Davidsson, P
    Vanmechelen, E
    Blennow, K
    Tau and Abeta42 in cerebrospinal fluid from healthy adults 21-93 years of age: establishment of reference values2001In: Clinical Chemistry, ISSN 0009-9147, E-ISSN 1530-8561, Vol. 47, p. 1776-1781Article in journal (Refereed)
  • 31.
    Öberg, Marie
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Technical Audiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Reconstruction Centre, Department of ENT - Head and Neck Surgery UHL.
    Marcusson, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Geriatric. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine.
    Nägga, Katarina
    Linköping University, Department of Clinical and Experimental Medicine, Geriatric. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine. Linköping University, Faculty of Health Sciences.
    Wressle, Ewa
    Linköping University, Department of Clinical and Experimental Medicine, Geriatric. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine.
    ELSA-85 en kartläggning av 85-åringars subjektiva hörsel och hörapparatanvändning2009Conference paper (Other academic)
  • 32.
    Öberg, Marie
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Technical Audiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of ENT - Head and Neck Surgery UHL.
    Marcusson, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Geriatric. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine.
    Nägga, Katarina
    Linköping University, Department of Clinical and Experimental Medicine, Geriatric. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine.
    Wressle, Ewa
    Linköping University, Department of Clinical and Experimental Medicine, Geriatric. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine.
    Hearing difficulties, uptake and outcomes of hearing aids in people 85 years of age2012In: International Journal of Audiology, ISSN 1499-2027, E-ISSN 1708-8186, Vol. 51, no 2, p. 108-115Article in journal (Refereed)
    Abstract [en]

    Objective: The aim of this study was to investigate self-reported hearing difficulties, uptake, and hearing-aid outcomes and their relationships to demographic, cognitive, psychosocial, and health variables in 85 year olds. Design and study sample: Three hundred and forty-six elderly adults participated in a survey that included questionnaires and home visits. Fifty-five percent of participants admitted to having hearing difficulties, and 59% of these owned hearing aids. The participants most frequently cited reason for not acquiring hearing aids was that they did not think their hearing problem was perceived as severe enough. Participants with hearing difficulties who did not own hearing aids showed worse general and mental health. Many of the elderly participants were successful in their rehabilitation, and their hearing-aid outcomes were similar to those of a younger group, with the exception of a greater proportion of non-users among the elderly. Conclusion: Many older people with self-reported hearing difficulties do not acquire hearing aids, despite this studys findings that older people are likely to have success with hearing rehabilitation. It is important to make greater efforts to try to increase elderly adults awareness of hearing loss and the benefits of hearing rehabilitation.

  • 33.
    Öberg, Marie
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Technical Audiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Reconstruction Centre, Department of ENT - Head and Neck Surgery UHL.
    Marcusson, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Geriatric. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in the East of Östergötland, Department of Geriatrics.
    Nägga, Katarina
    Linköping University, Department of Clinical and Experimental Medicine, Geriatric. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine.
    Wressle, Ewa
    Linköping University, Department of Clinical and Experimental Medicine, Geriatric. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine. Linköping University, Faculty of Health Sciences.
    Overall health related to subjective hearing loss and hearing aid uptake in an 85 year old Swedish population2009In: Hearing Care for Adult 2009-The challenge of Aging. Nov 16-18 ,2009 Chicago, USA, Chicago, 2009Conference paper (Refereed)
  • 34.
    Öberg, Marie
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Technical Audiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of ENT - Head and Neck Surgery UHL.
    Marcusson, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Geriatric. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine.
    Nägga, Katarina
    Linköping University, Department of Clinical and Experimental Medicine, Geriatric. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine.
    Wressle, Ewa
    Linköping University, Department of Clinical and Experimental Medicine, Geriatric. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine.
    Overall health related to subjective hearing loss and hearing uptake in an 85 year old Swedish population2011Conference paper (Other academic)
1 - 34 of 34
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