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  • 1.
    Borland, Emma
    et al.
    Lund University, Malmö, Sweden; Skåne University Hospital, Sweden.
    Nägga, Katarina
    Lund University, Malmö, Sweden.
    Nilsson, Peter M
    Lund University, Malmö, Sweden.
    Minthon, Lennart
    Lund University, Malmö, Sweden.
    Nilsson, Erik D
    Lund University, Malmö, Sweden.
    Palmqvist, Sebastian
    Lund University, Malmö, Sweden; Skåne University Hospital, Sweden.
    The Montreal Cognitive Assessment: Normative Data from a Large Swedish Population-Based Cohort.2017In: Journal of Alzheimer's Disease, ISSN 1387-2877, E-ISSN 1875-8908, Vol. 59, no 3, p. 893-901Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The Montreal Cognitive Assessment (MoCA) has a high sensitivity for detecting cognitive dysfunction. Swedish normative data does not exist and international norms are often derived from populations where cognitive impairment has not been screened for and not been thoroughly assessed to exclude subjects with dementia or mild cognitive impairment.

    OBJECTIVE: To establish norms for MoCA and develop a regression-based norm calculator based on a large, well-examined cohort.

    METHODS: MoCA was administered on 860 randomly selected elderly people from a population-based cohort from the EPIC study. Cognitive dysfunction was screened for and further assessed at a memory clinic. After excluding cognitively impaired participants, normative data was derived from 758 people, aged 65-85.

    RESULTS: MoCA cut-offs (-1 to -2 standard deviations) for cognitive impairment ranged from <25 to <21 for the lowest educated and <26 to <24 for the highest educated, depending on age group. Significant predictors for MoCA score were age, sex and level of education.

    CONCLUSION: We present detailed normative MoCA data and cut-offs according to the DSM-5 criteria for cognitive impairment based on a large population-based cohort of elderly individuals, screened and thoroughly investigated to rule out cognitive impairment. Level of education, sex, and age should be taken in account when evaluating MoCA score, which is facilitated by our online regression-based calculator that provide percentile and z-score for a subject's MoCA score.

  • 2.
    Gustavsson, Anna-Märta
    et al.
    Lund University, Malmö, Sweden.
    Stomrud, Erik
    Lund University, Malmö, Sweden.
    Abul-Kasim, Kasim
    Lund University, Malmö, Sweden.
    Minthon, Lennart
    Lund University, Malmö, Sweden.
    Nilsson, Peter M
    Lund University, Malmö, Sweden.
    Hansson, Oskar
    Lund University, Malmö, Sweden.
    Nägga, Katarina
    Lund University, Malmö, Sweden.
    Cerebral Microbleeds and White Matter Hyperintensities in Cognitively Healthy Elderly: A Cross-Sectional Cohort Study Evaluating the Effect of Arterial Stiffness2015In: Central and Eastern European Migration Review, ISSN 1664-5456, E-ISSN 2053-8871, Vol. 5, no 2, p. 41-51Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Arterial stiffness reflects the ageing processes in the vascular system, and studies have shown an association between reduced cognitive function and cerebral small vessel disease. Small vessel disease can be visualized as white matter hyperintensities (WMH) and lacunar infarcts but also as cerebral microbleeds on brain magnetic resonance imaging (MRI). We aimed to investigate if arterial stiffness influences the presence of microbleeds, WMH and cognitive function in a population of cognitively healthy elderly.

    METHODS: The study population is part of the Swedish BioFinder study and consisted of 208 individuals without any symptoms of cognitive impairment, who scored >27 points on the Mini-Mental State Examination. The participants (mean age, 72 years; 59% women) underwent MRI of the brain with visual rating of microbleeds and WMH. Arterial stiffness was measured with carotid-femoral pulse wave velocity (cfPWV). Eight cognitive tests covering different cognitive domains were performed.

    RESULTS: Microbleeds were detected in 12% and WMH in 31% of the participants. Mean (±standard deviation, SD) cfPWV was 10.0 (±2.0) m/s. There was no association between the presence of microbleeds and arterial stiffness. There was a positive association between arterial stiffness and WMH independent of age or sex (odds ratio, 1.58; 95% confidence interval, 1.04-2.40, p < 0.05), but the effect was attenuated when further adjustments for several cardiovascular risk factors were performed (p > 0.05). Cognitive performance was not associated with microbleeds, but individuals with WMH performed slightly worse than those without WMH on the Symbol Digit Modalities Test (mean ± SD, 35 ± 7.8 vs. 39 ± 8.1, p < 0.05). Linear regression revealed no direct associations between arterial stiffness and the results of the cognitive tests.

    CONCLUSIONS: Arterial stiffness was not associated with the presence of cerebral microbleeds or cognitive function in cognitively healthy elderly. However, arterial stiffness was related to the presence of WMH, but the association was attenuated when multiple adjustments were made. There was a weak negative association between WMH and performance in one specific test of attention. Longitudinal follow-up studies are needed to further assess the associations.

  • 3.
    Hall, Sara
    et al.
    Lund University, Lund, Sweden.
    Öhrfelt, Annika
    The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
    Constantinescu, Radu
    Sahlgrenska University Hospital.
    Andreasson, Ulf
    The Sahlgrenska Academy at University of Gothenburg.
    Surova, Yulia
    Lund University, Lund, Sweden; Skåne University Hospital, Malmö/Lund, Sweden.
    Bostrom, Frederick
    Lund University, Lund, Sweden; Skåne University Hospital, Malmö/Lund, Sweden.
    Nilsson, Christer
    Skåne University Hospital, Malmö/Lund, Sweden.
    Widner, Håkan
    Lund University, Lund, Sweden; Skåne University Hospital, Malmö/Lund, Sweden.
    Decraemer, Hilde
    Innogenetics, Gent, Belgium.
    Nägga, Katarina
    Lund University, Lund, Sweden; Skåne University Hospital, Malmö/Lund, Sweden.
    Minthon, Lennart
    Lund University, Lund, Sweden; Skåne University Hospital, Malmö/Lund, Sweden.
    Londos, Elisabet
    Lund University, Lund, Sweden; Skåne University Hospital, Malmö/Lund, Sweden.
    Vanmechelen, Eugeen
    Innogenetics, Gent, Belgium.
    Holmberg, Björn
    Sahlgrenska University Hospital, Gothenburg, Sweden.
    Zetterberg, Henrik
    Sahlgrenska University Hospital, Gothenburg, Sweden.
    Blennow, Kaj
    Sahlgrenska University Hospital, Gothenburg, Sweden.
    Hansson, Oskar
    Lund University, Lund, Sweden; Skåne University Hospital, Malmö/Lund, Sweden.
    Accuracy of a panel of 5 cerebrospinal fluid biomarkers in the differential diagnosis of patients with dementia and/or parkinsonian disorders2012In: Archives of Neurology, ISSN 0003-9942, E-ISSN 1538-3687, Vol. 69, no 11, p. 1445-1452Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To assess the ability of 5 cerebrospinal fluid(CSF) biomarkers to differentiate between common dementia and parkinsonian disorders.

    DESIGN: A cross-sectional, clinic-based study.

    PARTICIPANTS: Cerebrospinal fluid samples (N=453) were obtained from healthy individuals serving as controls and from patients with Parkinson disease (PD), PD with dementia(PDD), dementia with Lewy bodies (DLB), Alzheimer disease (AD), progressive supranuclear palsy(PSP), multiple system atrophy (MSA), or corticobasal degeneration (CBD).

    SETTING: Neurology and memory disorder clinics.

    MAIN OUTCOME MEASURES: Cerebrospinal fluid biomarker levels in relation to clinical diagnosis.

    RESULTS: Cerebrospinal fluid levels of -synuclein were decreased in patients with PD, PDD, DLB, and MSA but increased in patients with AD. Cerebrospinal fluid levels of α-amyloid 1-42 were decreased in DLB and even further decreased in AD. Cerebrospinal fluid levels of total tau and hyperphosphorylated tau were increased in AD. Multivariate analysis revealed that these biomarkers could differentiate AD from DLB and PDD with an area under the curve of 0.90, with -synuclein and total tau contributing most to the model. Cerebrospinal fluid levels of neurofilament light chain were substantially increased in atypical parkinsonian disorders (ie, PSP, MSA,and CBD), and multivariate analysis revealed that the level of neurofilament light chain alone could differentiate PD from atypical parkinsonian disorders, with an area under the curve of 0.93.

    CONCLUSIONS: Ascertainment of the -synuclein level in CSF somewhat improves the differential diagnosis of AD vs DLB and PDD when combined with established AD biomarkers.The level of neurofilament light chain alone may differentiate PD from atypical parkinsonian disorders.

  • 4.
    Holm, Hannes
    et al.
    Lund University, Malmö, Sweden; Skåne University Hospital, Malmö, Sweden.
    Nägga, Katarina
    Lund University, Malmö, Sweden.
    Nilsson, Erik D
    Lund University, Malmö, Sweden.
    Melander, Olle
    Lund University, Malmö, Sweden; Skåne University Hospital, Malmö, Sweden.
    Minthon, Lennart
    Lund University, Malmö, Sweden.
    Bachus, Erasmus
    Lund University, Malmö, Sweden; Skåne University Hospital, Malmö, Sweden.
    Fedorowski, Artur
    Lund University, Malmö, Sweden; Skåne University Hospital, Malmö, Sweden.
    Magnusson, Martin
    Lund University, Malmö, Sweden; Skåne University Hospital, Malmö, Sweden.
    Longitudinal and postural changes of blood pressure predict dementia: the Malmö Preventive Project2017In: European Journal of Epidemiology, ISSN 0393-2990, E-ISSN 1573-7284, Vol. 32, no 4, p. 327-336Article in journal (Refereed)
    Abstract [en]

    The role of blood pressure (BP) changes in dementia is debatable. We aimed to analyse how resting and postural BP changes relate to incident dementia over a long-term follow-up. In the prospective population-based Malmö Preventive Project, 18,240 study participants (mean age: 45 ± 7 years, 63% male) were examined between 1974 and 1992 with resting and standing BP measurement, and re-examined between 2002 and 2006 at mean age of 68 ± 6 years with resting BP. A total of 428 participants (2.3%) were diagnosed with dementia through Dec 31, 2009. The association of resting and postural BP changes with risk of dementia was studied using multivariable-adjusted Cox regression models controlling for traditional risk factors. Diastolic BP (DBP) decrease on standing indicated higher risk of dementia [Hazard ratio (HR) per 10 mmHg: 1.22; 95% confidence interval (CI) 1.01-1.44, p = 0.036], which was mainly driven by increased risk in normotensive individuals. Higher systolic (SBP) and diastolic BP at re-examination was associated with lower risk of dementia (HR per 10 mmHg: 0.94; 95% CI 0.89-0.99, p = 0.011; and 0.87; 0.78-0.96, p = 0.006, respectively). Extreme decrease in SBP/DBP between baseline and re-examination (4th quartile; -7 ± 12/-15 ± 7 mmHg, respectively) indicated higher risk of dementia (HR 1.46; 95% CI 1.11-1.93, p = 0.008, and 1.54; 95% CI 1.14-2.08, p = 0.005; respectively) compared with reference group characterised by pronounced BP increase over the same period (1st quartile; +44 ± 13/+15 ± 7 mmHg). Diastolic BP decrease on standing in the middle age, decline in BP between middle-and advanced age, and lower BP in advanced age are independent risk factors of developing dementia.

  • 5.
    Holm, Hannes
    et al.
    Lund University, Lund, Sweden; Skåne University Hospital, Lund, Sweden.
    Nägga, Katarina
    Lund University, Lund, Sweden.
    Nilsson, Erik D
    Lund University, Lund, Sweden.
    Ricci, Fabrizio
    University G. d'Annunzio, Chieti, Italy.
    Cinosi, Eduardo
    Foundation G. d'Annunzio, Chieti, Italy; NHS Hertfordshire Partnership University Foundation Trust, Hatfield, UK.
    Melander, Olle
    Lund University, Lund, Sweden; Skåne University Hospital, Lund, Sweden.
    Hansson, Oskar
    Lund University, Lund, Sweden.
    Bachus, Erasmus
    Lund University, Lund, Sweden; Skåne University Hospital, Lund, Sweden.
    Magnusson, Martin
    Lund University, Lund, Sweden; Skåne University Hospital, Malmö, Sweden.
    Fedorowski, Artur
    Lund University, Lund, Sweden; Skåne University Hospital, Malmö, Sweden.
    N-Terminal Prosomatostatin and Risk of Vascular Dementia2017In: Cerebrovascular Diseases, ISSN 1015-9770, E-ISSN 1421-9786, Vol. 44, no 5-6, p. 259-265Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Increased somatostatin plasma concentration has been found in patients with vascular dementia. However, it is unknown whether or not somatostatin levels may predict dementia development in the general population. To this end, we sought to assess the association of circulating N-terminal prosomatostatin (NT-proSST) with incident dementia among community-dwelling older adults.

    METHODS: In the prospective population-based Malmö Preventive Project, 5,347 study participants (mean age: 69 ± 6years; 70% men) provided plasma for the determination of NT-proSST concentration. Of these, 373 participants (7%) were diagnosed with dementia (120 Alzheimer's disease, 83 vascular, 102 mixed, and 68 other aetiology) during a follow-up period of 4.6 ± 1.3 years. The association of NT-proSST with the risk of dementia and its subtypes was studied using multivariable-adjusted Cox regression models controlling for age, gender, body mass index, systolic blood pressure, antihypertensive treatment, smoking, diabetes, lipid levels and prevalent stroke.

    RESULTS: Higher levels of NT-proSST were significantly associated with an increased risk of vascular dementia (hazard ratio [HR] per 1 SD: 1.29; 95% CI 1.05-1.59; p = 0.016), whereas no association was observed with Alzheimer's disease (HR per 1 SD: 0.99; 95% CI 0.81-1.20; p = 0.91), all-cause dementia (HR per 1 SD: 1.04; 95% CI 0.94-1.16; p = 0.44), and mixed dementia (HR per 1 SD: 0.98; 95% CI 0.79-1.21; p = 0.84). Levels of NT-proSST above 563 pmol/L (highest quartile) conferred distinctly increased risk of vascular dementia (HR 1.66; 95% CI 1.05-2.63; p = 0.029) compared with lower values.

    CONCLUSIONS: Higher levels of circulating N-terminal-prosomatostatin are associated with increased incidence of vascular dementia. Our findings might be of importance for the understanding of dementia development in older adults.

  • 6. Hölttä, Mikko
    et al.
    Hansson, Oskar
    Andreasson, Ulf
    Hertze, Joakim
    Minthon, Lennart
    Nägga, Katarina
    Enheten för Klinisk Minnesforskning, Institutionen för Kliniska Vetenskaper Malmö, Lunds Universitet.
    Andreasen, Niels
    Zetterberg, Henrik
    Blennow, Kaj
    Evaluating amyloid-β oligomers in cerebrospinal fluid as a biomarker for Alzheimer's disease.2013In: PLoS ONE, E-ISSN 1932-6203, Vol. 8, no 6, article id e66381Article in journal (Refereed)
    Abstract [en]

    The current study evaluated amyloid-β oligomers (Aβo) in cerebrospinal fluid as a clinical biomarker for Alzheimer's disease (AD). We developed a highly sensitive Aβo ELISA using the same N-terminal monoclonal antibody (82E1) for capture and detection. CSF samples from patients with AD, mild cognitive impairment (MCI), and healthy controls were examined. The assay was specific for oligomerized Aβ with a lower limit of quantification of 200 fg/ml, and the assay signal showed a tight correlation with synthetic Aβo levels. Three clinical materials of well characterized AD patients (n = 199) and cognitively healthy controls (n = 148) from different clinical centers were included, together with a clinical material of patients with MCI (n = 165). Aβo levels were elevated in the all three AD-control comparisons although with a large overlap and a separation from controls that was far from complete. Patients with MCI who later converted to AD had increased Aβo levels on a group level but several samples had undetectable levels. These results indicate that presence of high or measurable Aβo levels in CSF is clearly associated with AD, but the overlap is too large for the test to have any diagnostic potential on its own.

  • 7.
    Janelidze, Shorena
    et al.
    Lund University, Lund, Sweden.
    Hertze, Joakim
    Lund University, Lund, Sweden; Skåne University Hospital, Malmö, Sweden.
    Nägga, Katarina
    Lund University, Lund, Sweden; Skåne University Hospital, Malmö, Sweden.
    Nilsson, Karin
    Skåne University Hospital, Malmö, Sweden.
    Nilsson, Christer
    Lund University, Lund, Sweden; Skåne University Hospital, Lund, Sweden.
    Wennström, Malin
    Lund University, Wallenberg Laboratory, Malmö, Sweden.
    van Westen, Danielle
    Lund University, Lund, Sweden; Skåne University Health Care, Lund, Sweden.
    Blennow, Kaj
    the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden; Sahlgrenska University Hospital, Mölndal, Sweden.
    Zetterberg, Henrik
    the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden; Sahlgrenska University Hospital, Mölndal, Sweden; UCL Institute of Neurology, Queen Square, London, UK.
    Hansson, Oskar
    Lund University, Lund, Sweden; Skåne University Hospital, Malmö, Sweden.
    Increased blood-brain barrier permeability is associated with dementia and diabetes but not amyloid pathology or APOE genotype2017In: Neurobiology of Aging, ISSN 0197-4580, E-ISSN 1558-1497, Vol. 51, p. 104-112, article id S0197-4580(16)30304-9Article in journal (Refereed)
    Abstract [en]

    Blood-brain barrier (BBB) dysfunction might be an important component of many neurodegenerative disorders. In this study, we investigated its role in dementia using large clinical cohorts. The cerebrospinal fluid (CSF)/plasma albumin ratio (Qalb), an indicator of BBB (and blood-CSF barrier) permeability, was measured in a total of 1015 individuals. The ratio was increased in patients with Alzheimer's disease, dementia with Lewy bodies or Parkinson's disease dementia, subcortical vascular dementia, and frontotemporal dementia compared with controls. However, this measure was not changed during preclinical or prodromal Alzheimer's disease and was not associated with amyloid positron emission tomography or APOE genotype. The Qalb was increased in diabetes mellitus and correlated positively with CSF biomarkers of angiogenesis and endothelial dysfunction (vascular endothelial growth factor, intracellular adhesion molecule 1, and vascular cell adhesion molecule 1). In healthy elderly, high body mass index and waist-hip ratio predicted increased Qalb 20 years later. In summary, BBB permeability is increased in major dementia disorders but does not relate to amyloid pathology or APOE genotype. Instead, BBB impairment may be associated with diabetes and brain microvascular damage.

  • 8.
    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.
    Granvik, Eva
    Lund University, Lund, Sweden.
    Minthon, Lennart
    Lund University, Lund, Sweden.
    Nägga, Katarina
    Lund University, Lund, Sweden.
    Nishida, Atsushi
    Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan.
    Psychosocial behaviour management programme for home-dwelling people with dementia: A cluster-randomized controlled trial2018In: International Journal of Geriatric Psychiatry, ISSN 0885-6230, E-ISSN 1099-1166, Vol. 33, no 3, p. 495-503Article in journal (Refereed)
    Abstract [en]

    Little is known about the effectiveness of a psychosocial behaviour management programme on home-dwelling people with dementia. We developed a Behaviour Analytics & Support Enhancement (BASE) programme for care managers and professional caregivers of home care services in Japan. We investigated the effects of BASE on challenging behaviour of home-dwelling people with dementia.

    METHODS: A cluster-randomized controlled trial was conducted with home care providers from 3 different districts in Tokyo. Each provider recruited persons with dementia aged 65 years or older to receive home care in the BASE programme in August 2016. An online monitoring and assessment system was introduced to the intervention group for repeated measures of challenging behaviour with a total score of the Neuropsychiatric Inventory. Care professionals in both the intervention and control groups evaluated challenging behaviour of persons with dementia at baseline (September 2016) and follow-up (February 2017).

    RESULTS: A majority of persons with dementia had Alzheimer disease (59.3%). One-hundred and forty-one persons with dementia were included in the intervention group and 142 in the control group. Multilevel modelling revealed a significant reduction in challenging behaviour in the intervention group after 6 months (mean score, 18.3 to 11.2) compared with that of the control group (11.6 to 10.8; P < .05).

    CONCLUSION: The implementation of the BASE programme resulted in a reduction of challenging behaviour of home-dwelling people with dementia. Future research should examine the long-term effects of behaviour management programmes on behaviour, nursing home placement, and hospital admission of home-dwelling people with dementia.

  • 9.
    Nilsson, Erik D
    et al.
    Lund University, Lund, Sweden.
    Elmståhl, Sölve
    Skåne University Hospital, Malmö, Sweden.
    Minthon, Lennart
    Lund University, Lund, Sweden.
    Nilsson, Peter M
    Skåne University Hospital, Malmö, Sweden.
    Pihlsgård, Mats
    Skåne University Hospital, Malmö, Sweden.
    Tufvesson, Eva
    Lund University, Lund, Sweden.
    Nägga, Katarina
    Lund University, Lund, Sweden.
    Nonlinear association between pulse wave velocity and cognitive function: a population-based study2014In: Journal of Hypertension, ISSN 0263-6352, E-ISSN 1473-5598, Vol. 32, no 11, p. 2152-2157Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Arterial stiffness has been hypothesized to contribute to cognitive decline. However, previous studies have reported inconsistent results. The aim of this cross-sectional study was to investigate the association between carotid-femoral pulse wave velocity (cfPWV), a marker of arterial stiffness, and cognitive function.

    METHODS: The study population comprised 2637 individuals from the population-based Malmö Diet and Cancer Study (mean age 72.1 years, 60.8% women). During the follow-up examinations between 2007 and 2012, cfPWV and results on the a quick test of cognitive speed (AQT) and Mini Mental State Examination (MMSE) cognitive tests were measured.

    RESULTS: After adjustments for demographics and traditional cardiovascular risk factors, a linear association was found between cfPWV and AQT (B = 0.37; P = 0.039). On the basis of hypothesis that individuals with high cfPWV values have worse cognitive function than can be inferred from a linear association, cfPWV was dichotomized at the 90th percentile (the binary variable denoted cfPWV >13.8). When cfPWV >13.8 was added to the model, the linear association between continuous cfPWV and AQT disappeared (B = -0.08; P = 0.72), but cfPWV >13.8 was highly significant (B = 4.81; P = 0.004). In the adjusted model with MMSE as outcome variable, cfPWV >13.8 also reached a statistically significant effect.

    CONCLUSION: Arterial stiffness was inversely associated with cognitive function in a nonlinear fashion, with individuals in the top decentile of cfPWV explaining the association. Results from linear regressions should thus be interpreted with caution because, even when statistical significance is reached, they can be explained by pronounced nonlinearity.

  • 10.
    Nilsson, Erik D
    et al.
    Lund University, Malmö, Sweden.
    Elmståhl, Sölve
    Lund University, Lund, Sweden; Skåne University Hospital, Lund, Sweden.
    Minthon, Lennart
    Lund University, Malmö, Sweden.
    Pihlsgård, Mats
    Lund University, Lund, Sweden; Skåne University Hospital, Lund, Sweden.
    Nilsson, Peter M
    Skåne University Hospital, Lund, Sweden; Lund University, Lund, Sweden.
    Hansson, Oskar
    Lund University, Malmö, Sweden; Skåne University Hospital, Malmö, Sweden.
    Nägga, Katarina
    Lund University, Malmö, Sweden; Skåne University Hospital, Malmö, Sweden.
    No independent association between pulse wave velocity and dementia: a population-based, prospective study.2017In: Journal of Hypertension, ISSN 0263-6352, E-ISSN 1473-5598, Vol. 35, no 12, p. 2462-2467Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Carotid-femoral pulse wave velocity (CFPWV), a marker of aortic stiffness, has been associated with cognitive test results and markers of cerebral small vessel disease, but its association with dementia has not been studied in detail. Our aim was to assess the association of CFPWV with prevalent and incident dementia in a large population-based study.

    METHODS: In total, CFPWV was measured in 3056 participants of the Malmö Diet and Cancer study 2007-2012 (age range 61-85 years). Individuals scoring below preset cut-offs on cognitive screening tests were thoroughly evaluated for prevalent dementia. Also, dementia diagnoses were retrieved from the Swedish National Patient Register up until 31 December 2014, and then validated through medical records and neuroimaging findings.

    RESULTS: We identified 159 cases of dementia, of which 57 were classified as prevalent, and 102 as incident during a median follow-up of 4.6 years. In fully adjusted logistic regressions, CFPWV was not associated with prevalent all-cause dementia (odds ratio 0.95 per 1 m/s increase in CFPWV, 95% confidence interval 0.83-1.08), and it did not predict incident all-cause dementia (odds ratio 1.00, 95% confidence interval 0.91-1.09). Neither was CFPWV associated with subtypes of dementia (Alzheimer's disease, vascular dementia, mixed dementia), although the number of cases in subgroups were low.

    CONCLUSION: No independent association was found between CFPWV and dementia. It remains a matter of debate why CFPWV repeatedly has been associated with cognitive test results and markers of cerebral small vessel disease, but not with dementia.

  • 11.
    Nilsson, Erik D
    et al.
    Lund University, Malmö, Sweden.
    Melander, Olle
    Lund University, Lund, Sweden.
    Elmståhl, Sölve
    Lund University, Lund, Sweden.
    Lethagen, Eva
    Lund University, Malmö, Sweden.
    Minthon, Lennart
    Lund University, Malmö, Sweden.
    Pihlsgård, Mats
    Lund University, Lund, Sweden.
    Nägga, Katarina
    Lund University, Malmö, Sweden.
    Copeptin, a Marker of Vasopressin, Predicts Vascular Dementia but not Alzheimer's Disease2016In: Journal of Alzheimer's Disease, ISSN 1387-2877, E-ISSN 1875-8908, Vol. 52, no 3, p. 1047-1053Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Copeptin is a reliable surrogate marker for the neurohypophyseal hormone vasopressin. Elevated plasma level of copeptin has been associated with cardiovascular and metabolic disease risk.

    OBJECTIVE: To investigate the association between copeptin and risk of dementia.

    METHODS: In all, 18,240 individuals from Malmö, Sweden, were examined between 2002 and 2006 (mean age 69.3 years, 69.8% men). Incident cases of dementia until 31 December 2009 were identified by linkage with the Swedish National Patient Register. To validate the dementia diagnoses, medical records as well as laboratory and neuroimaging data were carefully reviewed. Baseline level of copeptin was measured in frozen plasma in: (1) all participants who were diagnosed with dementia during follow-up, (2) a random sample of 5100 individuals of the cohort.

    RESULTS: During a median follow-up of 4.2 years, there were 374 incident dementia cases (age range 60-83 years at baseline): 120 were classified as Alzheimer's disease (AD), 84 as vascular dementia (VaD), and 102 as mixed dementia. In logistic regressions adjusted for cardiovascular risk factors, baseline level of copeptin predicted incident VaD (Odds ratio (OR) 1.30 per 1 SD increase in log copeptin, 95% CI 1.03-1.64). Copeptin did not predict incidence of all-cause dementia (OR 1.05, 95% CI 0.94-1.18), AD (OR 0.97, 95% CI 0.79-1.18), or mixed dementia (OR 0.85, 95% CI 0.68-1.05).

    CONCLUSION: Elevated plasma level of copeptin is a risk marker for incident VaD, but not for incident AD. This suggests that the vasopressin hormonal system might be involved in the development of VaD.

  • 12. Nutu, Magdalena
    et al.
    Zetterberg, Henrik
    Londos, Elisabet
    Minthon, Lennart
    Nägga, Katarina
    Enheten för Klinisk Minnesforskning, Institutionen för Kliniska Vetenskaper Malmö, Lunds Universitet.
    Blennow, Kaj
    Hansson, Oskar
    Ohrfelt, Annika
    Evaluation of the cerebrospinal fluid amyloid-β1-42/amyloid-β1-40 ratio measured by alpha-LISA to distinguish Alzheimer's disease from other dementia disorders.2013In: Dementia and Geriatric Cognitive Disorders, ISSN 1420-8008, E-ISSN 1421-9824, Vol. 36, no 1-2, p. 99-110Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The well-established core biomarkers used to identify Alzheimer's disease (AD) overlap with other dementia disorders such as dementia with Lewy bodies (DLB) and Parkinson's disease with dementia (PDD). This study aimed to evaluate whether the cerebrospinal fluid (CSF) amyloid-β (Aβ)1-42/Aβ1-40 ratio, measured by a novel method, could improve the differential diagnosis of AD, DLB and PDD.

    METHOD: CSF levels of Aβ1-40 and Aβ1-42 in patients with PDD, DLB, AD, Parkinson's disease and controls were analyzed using an amplified luminescent proximity homogenous immunoassay along with conventional immunoassays.

    RESULTS: The CSF Aβ1-42/Aβ1-40 ratio increased discrimination of AD from PDD and DLB compared with either of the two Aβ biomarkers individually.

    CONCLUSION: The use of the Aβ1-42/Aβ1-40 ratio could improve the differentiation of AD from PDD and DLB.

  • 13.
    Nägga, Katarina
    et al.
    Lund University, Malmö, Sweden; Skåne University Hospital, Malmö, Sweden.
    Gustavsson, Anna-Märta
    Lund University, Malmö, Sweden; Skåne University Hospital, Malmö, Sweden.
    Stomrud, Erik
    Lund University, Malmö, Sweden; Skåne University Hospital, Malmö, Sweden.
    Lindqvist, Daniel
    Lund University, Malmö, Sweden.
    van Westen, Danielle
    Lund University, Malmö, Sweden.
    Blennow, Kaj
    The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden; Sahlgrenska University Hospital, Mölndal, Sweden.
    Zetterberg, Henrik
    The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden; Sahlgrenska University Hospital, Mölndal, Sweden; UCL Institute of Neurology, Queen Square, London, UK.
    Melander, Olle
    Lund University, Malmö, Sweden.
    Hansson, Oskar
    Lund University, Malmö, Sweden; Skåne University Hospital, Malmö, Sweden.
    Increased midlife triglycerides predict brain β-amyloid and tau pathology 20 years later2018In: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 90, no 1, p. e73-e81Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To evaluate the effect of midlife lipid levels on Alzheimer brain pathology 20 years later in cognitively normal elderly individuals.

    METHODS: This is a longitudinal cohort study of 318 cognitively normal individuals with data on fasting lipid levels at midlife (mean age 54 years). Presence of β-amyloid (Aβ) and tau pathologies 20 years later (mean age 73 years) were detected by quantifying Alzheimer disease (AD) biomarkers in CSF. In a subset (n = 134), Aβ (18F-flutemetamol) PET was also performed.

    RESULTS: CSF Aβ42 and Aβ PET revealed Aβ pathology in approximately 20% of the cognitively healthy population and CSF Aβ42/phosphorylated tau (p-tau) ratio indicated both Aβ and tau pathology in 16%. Higher levels of triglycerides in midlife were independently associated with abnormal CSF Aβ42 (odds ratio [OR] 1.34, 95% confidence interval [CI] 1.03-1.75, p = 0.029) and abnormal Aβ42/p-tau ratio (OR 1.46, 95% CI 1.10-1.93; p = 0.009) adjusting for age, sex, APOE ε4, education, and multiple vascular risk factors. Triglycerides were also associated with abnormal Aβ PET in multivariable regression models, but the association was attenuated in the fully adjusted model. Increased levels of medium and large low-density lipoprotein subfractions were significantly associated with abnormal Aβ PET and large high-density lipoprotein particles were associated with decreased risk of abnormal Aβ PET.

    CONCLUSIONS: Increased levels of triglycerides at midlife predict brain Aβ and tau pathology 20 years later in cognitively healthy individuals. Certain lipoprotein subfractions may also be risk factors for Aβ pathology. These findings further support an involvement of lipids in the very early stages of AD development.

  • 14.
    Nägga, Katarina
    et al.
    Lund University, Malmö, Sweden.
    Wattmo, Carina
    Lund University, Malmö, Sweden.
    Zhang, Yi
    Karolinska University Hospital, Stockholm, Sweden.
    Wahlund, Lars-Olof
    Karolinska University Hospital, Stockholm, Sweden.
    Palmqvist, Sebastian
    Lund University, Malmö, Sweden; Skåne University Hospital, Lund, Sweden.
    Cerebral inflammation is an underlying mechanism of early death in Alzheimer's disease: a 13-year cause-specific multivariate mortality study2014In: Alzheimer's Research & Therapy, E-ISSN 1758-9193, Alzheimer's research & therapy, ISSN 1758-9193, Vol. 6, no 4, article id 41Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: Although Alzheimer's disease (AD) is associated with early death, its life expectancy differs greatly between patients. A better understanding of this heterogeneity may reveal important disease mechanisms underlying the malignancy of AD. The aim of this study was to examine the relation between AD pathologies and early death in AD caused by dementia.

    METHODS: At a memory clinic, 247 referred consecutive patients with AD were monitored during 12.6 ± 1.6 years. Multivariate Cox regression analyses were performed with baseline measures of amyloid beta (Aβ) pathology (APOE genotype, cerebrospinal fluid (CSF) Aβ42) tau pathology (CSF phosphorylated tau and total tau), cerebrovascular pathology (white-matter lesions and CSF/serum albumin ratio), neuroinflammatory pathology (CSF soluble vascular cell adhesion molecule-1, sVCAM-1), frontal, temporal, and central brain atrophies, global cognition, sex, and age. Comorbidities and medications also were analyzed. All continuous variables were transformed to z scores to compare hazard ratios (HRs) and 95% confidence intervals (CIs).

    RESULTS: At follow-up, 89% of the patients had died. The mean survival time was 6.4 ± 3.0 years. The AD pathology that independently predicted an early death caused by dementia was cerebral inflammation (sVCAM-1; HR, 1.32; 95% CI, 1.07-1.64). Other independent predictors were lower global cognition (HR, 0.51; 95% CI, 0.43-0.61), frontal atrophy (HR, 1.38; 95% CI, 1.12-1.70), and medial temporal atrophy (HR, 1.23; 95% CI, 1.02-1.49). When examining death caused by dementia and related causes (vascular diseases and infections), age (HR, 1.23; 95% CI, 1.04-1.46) and cerebrovascular pathology (white-matter lesions: HR, 1.17; 95% CI, 1.01-1.36; and CSF/serum albumin ratio: HR, 1.16; 95% CI, 1.001-1.34) were also significant risk factors in addition to the previous variables. No comorbidity or medication was significant in the specific-cause models.

    CONCLUSIONS: This is the first study to link neuroinflammation independently to early death in AD and, hence, a rapidly progressing disease. Frontal and medial temporal atrophies and low cognition were also significant predictors. These are probably downstream biomarkers that reflect neuronal degeneration and late-stage disease. Our results suggest that inflammation, and not amyloid or tau pathology, is an independent underlying mechanism in the malignancy of AD.

  • 15.
    Oksengard, A R
    et al.
    Karolinska University Hospital, Stockholm, Sweden; Oslo University Hospital, Ullevål and Vestre Viken, Bærum, Norway.
    Cavallin, L
    Karolinska University Hospital, Stockholm, Sweden.
    Axelsson, R
    Karolinska University Hospital, Stockholm, Sweden.
    Andersson, C
    Karolinska Institute, Huddinge, Sweden.
    Nägga, Katarina
    Lund University, Malmö, Sweden.
    Winblad, B
    Karolinska Institute, Huddinge, Sweden.
    Eriksdotter-Jönhagen, M
    Karolinska University Hospital, Stockholm, Sweden.
    Wahlund, L O
    Karolinska University Hospital, Stockholm, Sweden.
    Lack of accuracy for the proposed 'Dubois criteria' in Alzheimer's disease: a validation study from the Swedish brain power initiative.2010In: Dementia and Geriatric Cognitive Disorders, ISSN 1420-8008, E-ISSN 1421-9824, Vol. 30, no 4, p. 374-380Article in journal (Refereed)
    Abstract [en]

    BACKGROUND/AIMS: Our purpose was to investigate whether the new research criteria for Alzheimer's disease proposed in 2007 by Dubois et al. are valid in a naturalistic memory clinic sample.

    METHOD: Retrospective diagnostic analyses were carried out to compare the traditional diagnostic criteria for dementia with the new criteria suggested by Dubois et al. No patient had gone through all procedures postulated as additional features in the proposed new Dubois criteria.

    MATERIAL: Two independent experienced geriatricians re-examined 150 complete patients' records. The study physicians were blinded to any of the results of the core and additional features suggested by Dubois et al. to avoid circular diagnostic bias.

    RESULTS: Among our 96 patients with a clinical diagnosis of subjective cognitive impairment and/or mild cognitive impairment, 2 of the patients with subjective cognitive impairment and 5 patients with mild cognitive impairment would classify as pre-dementia Alzheimer's disease according to the Dubois criteria. In our 23 Alzheimer patients diagnosed clinically, only 12 of the cases fulfilled the criteria for Alzheimer's disease suggested by Dubois et al.

    INTERPRETATION: The proposed new criteria for Alzheimer's disease are valid in 55% of our patients clinically diagnosed as having full-blown Alzheimer dementia. Additionally, 7.3% 'true' Alzheimer cases will be identified in a group of 96 clinically non-demented patients. Our results show that there is a large heterogeneity in a clinical naturalistic sample of patients with an Alzheimer phenotype.

    CONCLUSION: There is a need to further validate the currently existing biomarkers in large unselected samples and avoid the pitfall of workup bias and circular diagnostic processes. Additionally, valid age-specific cut-off values for the diagnostic markers in question have to be defined.

  • 16.
    Palmqvist, Sebastian
    et al.
    Lund University, Malmö, Sweden.
    Sarwari, Agmall
    Lund University, Malmö, Sweden.
    Wattmo, Carina
    Lund University, Malmö, Sweden.
    Bronge, Lena
    Karolinska University Hospital, Stockholm, Sweden.
    Zhang, Yi
    Karolinska University Hospital, Stockholm, Sweden.
    Wahlund, Lars Olof
    Karolinska University Hospital, Stockholm, Sweden.
    Nägga, Katarina
    Lund University, Malmö, Sweden.
    Association between subcortical lesions and behavioral and psychological symptoms in patients with Alzheimer's disease2011In: Dementia and Geriatric Cognitive Disorders, ISSN 1420-8008, E-ISSN 1421-9824, Vol. 32, no 6, p. 417-423Article in journal (Refereed)
    Abstract [en]

    BACKGROUND/AIMS: The most devastating features of Alz-heimer's disease (AD) are often the behavioral and psychological symptoms in dementia (BPSD). There is controversy as to whether subcortical lesions contribute to BPSD. The aim of this study was to examine the relationship between BPSD and subcortical lesions (white-matter lesions and lacunes) in AD.

    METHODS: CT or MRI from 259 patients with mild-to-moderate AD were assessed with the Age-Related White Matter Changes scale. Linear measures of global and temporal atrophy and Mini-Mental State Examination scores were used to adjust for AD pathology and disease severity in logistic regression models with the BPSD items delusions, hallucinations, agitation, depression, anxiety, apathy and irritability.

    RESULTS: Lacunes in the left basal ganglia were associated with delusions (OR 2.57, 95% CI 1.21-5.48) and hallucinations (OR 3.33, 95% CI 1.38-8.01) and lacunes in the right basal ganglia were associated with depression (OR 2.13, 95% CI 1.01-4.51).

    CONCLUSION: Lacunes in the basal ganglia resulted in a 2- to 3-fold increased risk of delusions, hallucinations and depression, when adjusting for cognition and atrophy. This suggests that basal ganglia lesions can contribute to BPSD in patients with AD, independently of the AD process.

  • 17.
    Palmqvist, Sebastian
    et al.
    Lund University, Lund, Sweden; Skåne University Hospital, Lund, Sweden.
    Zetterberg, Henrik
    the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden; the UCL Institute of Neurology, London, UK.
    Mattsson, Niklas
    the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden; University of California, San Francisco, USA; Center for Imaging of Neurodegenerative Diseases, San Francisco, CA, USA.
    Johansson, Per
    Sahlgrenska Academy, University of Gothenburg, Sweden.
    Minthon, Lennart
    Lund University, Lund, Sweden; Skåne University Hospital, Lund, Sweden.
    Blennow, Kaj
    the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
    Olsson, Mattias
    Lund University, Lund, Sweden.
    Hansson, Oskar
    Lund University, Lund, Sweden; Skåne University Hospital, Lund, Sweden.
    Detailed comparison of amyloid PET and CSF biomarkers for identifying early Alzheimer disease2015In: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 85, no 14, p. 1240-1249Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To compare the diagnostic accuracy of CSF biomarkers and amyloid PET for diagnosing early-stage Alzheimer disease (AD).

    METHODS: From the prospective, longitudinal BioFINDER study, we included 122 healthy elderly and 34 patients with mild cognitive impairment who developed AD dementia within 3 years (MCI-AD). β-Amyloid (Aβ) deposition in 9 brain regions was examined with [18F]-flutemetamol PET. CSF was analyzed with INNOTEST and EUROIMMUN ELISAs. The results were replicated in 146 controls and 64 patients with MCI-AD from the Alzheimer's Disease Neuroimaging Initiative study.

    RESULTS: The best CSF measures for identifying MCI-AD were Aβ42/total tau (t-tau) and Aβ42/hyperphosphorylated tau (p-tau) (area under the curve [AUC] 0.93-0.94). The best PET measures performed similarly (AUC 0.92-0.93; anterior cingulate, posterior cingulate/precuneus, and global neocortical uptake). CSF Aβ42/t-tau and Aβ42/p-tau performed better than CSF Aβ42 and Aβ42/40 (AUC difference 0.03-0.12, p<0.05). Using nonoptimized cutoffs, CSF Aβ42/t-tau had the highest accuracy of all CSF/PET biomarkers (sensitivity 97%, specificity 83%). The combination of CSF and PET was not better than using either biomarker separately.

    CONCLUSIONS: Amyloid PET and CSF biomarkers can identify early AD with high accuracy. There were no differences between the best CSF and PET measures and no improvement when combining them. Regional PET measures were not better than assessing the global Aβ deposition. The results were replicated in an independent cohort using another CSF assay and PET tracer. The choice between CSF and amyloid PET biomarkers for identifying early AD can be based on availability, costs, and doctor/patient preferences since both have equally high diagnostic accuracy.

    CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that amyloid PET and CSF biomarkers identify early-stage AD equally accurately.

  • 18.
    Rosén, Christoffer
    et al.
    The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
    Farahmand, Bahman
    Karolinska Institutet, Stockholm, Sweden; Karolinska University Hospital, Huddinge, Sweden.
    Skillbäck, Tobias
    The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
    Nägga, Katarina
    Lund University, Malmö, Sweden.
    Mattsson, Niklas
    The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden; University of California San Francisco, San Francisco, CA, USA.
    Kilander, Lena
    Uppsala University, Uppsala, Sweden.
    Religa, Dorota
    Karolinska University Hospital, Huddinge, Sweden; Karolinska Institutet, Huddinge, Sweden.
    Wimo, Anders
    Karolinska Institutet, Huddinge, Sweden.
    Blennow, Kaj
    The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
    Winblad, Bengt
    Karolinska University Hospital, Huddinge, Sweden; Karolinska Institutet, Huddinge, Sweden.
    Zetterberg, Henrik
    The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden; UCL Institute of Neurology, London, UK.
    Eriksdotter, Maria
    Karolinska Institutet, Stockholm, Sweden; Karolinska University Hospital, Huddinge, Sweden.
    Benchmarking biomarker-based criteria for Alzheimer's disease: Data from the Swedish Dementia Registry, SveDem.2015In: Alzheimer's & Dementia, ISSN 1552-5260, E-ISSN 1552-5279, Vol. 11, no 12, p. 1470-1479, article id S1552-5260(15)00185-5Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: New research guidelines for the diagnosis of Alzheimer's disease (AD) include biomarker evidence of amyloid-β (Aβ) and tau pathology. The aim of this study was to investigate what proportion of AD patients diagnosed in clinical routine in Sweden that had an AD-indicative cerebrospinal fluid (CSF) biomarker profile.

    METHODS: By cross-referencing a laboratory database with the Swedish Dementia Registry (SveDem), 2357 patients with data on CSF Aβ and tau biomarkers and a clinical diagnosis of AD with dementia were acquired.

    RESULTS: Altogether, 77.2% had pathologic Aβ42 and total tau or phosphorylated tau in CSF. These results were stable across age groups. Female sex and low mini-mental state examination score increased the likelihood of pathologic biomarkers.

    DISCUSSION: About a quarter of clinically diagnosed AD patients did not have an AD-indicative CSF biomarker profile. This discrepancy may partly reflect incorrect (false positive) clinical diagnosis or a lack in sensitivity of the biomarker assays.

  • 19.
    Skillbäck, Tobias
    et al.
    The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden; Sahlgrenska University Hospital, Mölndal, Sweden.
    Lautner, Ronald
    The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden; Sahlgrenska University Hospital, Mölndal, Sweden.
    Mattsson, Niklas
    Lund University, Malmö, Sweden; Skåne University Hospital, Lund, Sweden.
    Schott, Jonathan M
    Dementia Research Centre, UCL Institute of Neurology, London, UK.
    Skoog, Ingmar
    Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
    Nägga, Katarina
    Lund University, Malmö, Sweden.
    Kilander, Lena
    Uppsala University, Uppsala, Sweden.
    Wimo, Anders
    Karolinska Institutet, Huddinge, Sweden; Uppsala University/County Council of Gävleborg, Gävle, Sweden.
    Winblad, Bengt
    Karolinska Institutet, Huddinge, Sweden; Karolinska University Hospital, Huddinge, Sweden.
    Eriksdotter, Maria
    Karolinska Institutet, Huddinge, Sweden; Karolinska University Hospital, Huddinge, Sweden.
    Blennow, Kaj
    The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden; Sahlgrenska University Hospital, Mölndal, Sweden.
    Zetterberg, Henrik
    The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden; Sahlgrenska University Hospital, Mölndal, Sweden; UCL Institute of Neurology, Queen Square, London, UK.
    Apolipoprotein E genotypes and longevity across dementia disorders2018In: Alzheimer's & Dementia, ISSN 1552-5260, E-ISSN 1552-5279, Vol. 14, no 7, p. 895-901, article id S1552-5260(18)30045-1Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: The ε4 allele of the apolipoprotein E (APOE) gene is a prominent risk factor for Alzheimer's disease (AD), but its implication in other dementias is less well studied.

    METHODS: We used a data set on 2858 subjects (1098 AD, 260 vascular dementia [VaD], 145 mixed AD and VaD, 90 other dementia diagnoses, and 1265 controls) to examine the association of APOE polymorphisms with clinical dementia diagnoses, biomarker profiles, and longevity.

    RESULTS: The ε4 allele was associated with reduced longevity as ε4 versus ε3 homozygotes lived on average 2.6 years shorter (P = .006). In AD, ε4 carriers lived 1.0 years shorter than noncarriers (P = .028). The ε4 allele was more prevalent in AD, mixed AD and VaD, and VaD patients compared to controls, but not in other dementia disorders.

    DISCUSSION: The APOE ε4 allele is influential in AD but might also be of importance in VaD and in mixed AD and VaD, diseases in which concomitant AD pathology is common.

  • 20. Tufvesson, Eva
    et al.
    Melander, Olle
    Minthon, Lennart
    Persson, Margaretha
    Nilsson, Peter M
    Struck, Joachim
    Nägga, Katarina
    Enheten för Klinisk Minnesforskning, Institutionen för Kliniska Vetenskaper Malmö, Lunds Universitet.
    Diabetes mellitus and elevated copeptin levels in middle age predict low cognitive speed after long-term follow-up.2013In: Dementia and Geriatric Cognitive Disorders, ISSN 1420-8008, E-ISSN 1421-9824, Vol. 35, no 1-2, p. 67-76Article in journal (Refereed)
    Abstract [en]

    BACKGROUND/AIMS: We examined the potential impact of vascular risk factors including copeptin - a robust surrogate marker of arginine vasopressin associated with the metabolic syndrome and diabetes risk - on future cognitive abilities in a population-based cohort.

    METHODS: Participants (n = 933) were investigated using baseline data, including copeptin levels, and data collected 16 years later using the Mini-Mental State Examination (MMSE) and A Quick Test of Cognitive Speed (AQT).

    RESULTS: Logistic regression showed that diabetes (OR, 1.86; p < 0.05) and higher copeptin levels (OR, 1.19; p < 0.05) were independently associated with an increased risk of low AQT performance.

    CONCLUSION: Prevalence of diabetes mellitus and elevated copeptin levels in middle age predict lower cognitive speed after long-term follow-up.

  • 21.
    van Westen, Danielle
    et al.
    Lund University, Lund, Sweden; Skåne University Health Care, Lund, Sweden.
    Lindqvist, Daniel
    Lund University, Lund, Sweden; Division of Psychiatry Skåne, Lund, Sweden.
    Blennow, Kaj
    The Sahlgrenska Academy at University of Gothenburg, Mölndal, Sweden.
    Minthon, Lennart
    Lund University, Lund, Sweden; Skåne University Health Care, Lund, Sweden.
    Nägga, Katarina
    Lund University, Lund, Sweden; Skåne University Health Care, Lund, Sweden.
    Stomrud, Erik
    Lund University, Lund, Sweden; Skåne University Health Care, Lund, Sweden.
    Zetterberg, Henrik
    The Sahlgrenska Academy at University of Gothenburg, Mölndal, Sweden; UCL Institute of Neurology, Queen Square, London, United Kingdom.
    Hansson, Oskar
    Lund University, Lund, Sweden; Skåne University Health Care, Lund, Sweden.
    Cerebral white matter lesions: associations with Aβ isoforms and amyloid PET2016In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, article id 20709Article in journal (Refereed)
    Abstract [en]

    Small vessel disease (SVD) and amyloid deposition may promote each other, with a potential association between SVD and altered production or clearance of β-amyloid (Aβ) affecting its cleavage products. We investigated the relationship between SVD, multiple isoforms of Aβ in cerebrospinal fluid (CSF) and cortical Aβ in 831 subjects with cognitive performance ranging from normal to Alzheimer's disease (AD) (the Swedish BioFINDER study). SVD was estimated as white matter lesions (WML) and lacunes. 18F-flutemetamol PET was performed in 321 subjects. Lower CSF levels of Aβ38 and Aβ40 were consistently associated with increased WML in all subgroups, while lower levels of CSF Aβ42 were associated with WML mainly in AD. CSF Aβ38 and Aβ40 were associated with regional WML in all regions, while CSF Aβ42 was associated with temporal WML only. A composite measure of 18F-flutemetamol uptake was not associated with WML, and regional 18F-flutemetamol uptake only with temporal WML. Lacunes were not associated with Aβ isoforms nor 18F-flutemetamol uptake. Our results suggest that WML may be associated with alterations in the production or clearance of Aβ species, particularly of Aβ38 and Aβ40. However, in AD cases, Aβ42 pathology might be associated with WML, especially in the temporal lobe.

  • 22.
    Voevodskaya, Olga
    et al.
    Karolinska Institute, Stockholm, Sweden.
    Sundgren, Pia C
    Lund University, Lund, Sweden.
    Strandberg, Olof
    Lund University, Lund, Sweden.
    Zetterberg, Henrik
    the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden; UCL Institute of Neurology, Queen Square, London, UK.
    Minthon, Lennart
    Skåne University Hospital, Lund, Sweden; Lund University, Malmö, Sweden.
    Blennow, Kaj
    the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
    Wahlund, Lars-Olof
    Karolinska Institute, Stockholm, Sweden.
    Westman, Eric
    Karolinska Institute, Stockholm, Sweden.
    Hansson, Oskar
    Skåne University Hospital, Lund, Sweden; Lund University, Malmö, Sweden.
    Myo-inositol changes precede amyloid pathology and relate to APOE genotype in Alzheimer disease2016In: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 86, no 19, p. 1754-1761Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: We aimed to test whether in vivo levels of magnetic resonance spectroscopy (MRS) metabolites myo-inositol (mI), N-acetylaspartate (NAA), and choline are abnormal already during preclinical Alzheimer disease (AD), relating these changes to amyloid or tau pathology, and functional connectivity.

    METHODS: In this cross-sectional multicenter study (a subset of the prospective Swedish BioFINDER study), we included 4 groups, representing the different stages of predementia AD: (1) cognitively healthy elderly with normal CSF β-amyloid 42 (Aβ42), (2) cognitively healthy elderly with abnormal CSF Aβ42, (3) patients with subjective cognitive decline and abnormal CSF Aβ42, (4) patients with mild cognitive decline and abnormal CSF Aβ42 (Ntotal = 352). Spectroscopic markers measured in the posterior cingulate/precuneus were considered alongside known disease biomarkers: CSF Aβ42, phosphorylated tau, total tau, [(18)F]-flutemetamol PET, f-MRI, and the genetic risk factor APOE.

    RESULTS: Amyloid-positive cognitively healthy participants showed a significant increase in mI/creatine and mI/NAA levels compared to amyloid-negative healthy elderly (p < 0.05). In amyloid-positive healthy elderly, mI/creatine and mI/NAA correlated with cortical retention of [(18)F] flutemetamol tracer ([Formula: see text] = 0.44, p = 0.02 and [Formula: see text] = 0.51, p = 0.01, respectively). Healthy elderly APOE ε4 carriers with normal CSF Aβ42 levels had significantly higher mI/creatine levels (p < 0.001) than ε4 noncarriers. Finally, elevated mI/creatine was associated with decreased functional connectivity within the default mode network (rpearson = -0.16, p = 0.02), independently of amyloid pathology.

    CONCLUSIONS: mI levels are elevated already at asymptomatic stages of AD. Moreover, mI/creatine concentrations were increased in healthy APOE ε4 carriers with normal CSF Aβ42 levels, suggesting that mI levels may reveal regional brain consequences of APOE ε4 before detectable amyloid pathology.

  • 23.
    Wennström, Malin
    et al.
    Lund University, Malmö, Sweden.
    Hall, Sara
    Lund University, Malmö, Sweden.
    Nägga, Katarina
    Lund University, Malmö, Sweden.
    Londos, Elisabet
    Lund University, Malmö, Sweden.
    Minthon, Lennart
    Lund University, Malmö, Sweden.
    Hansson, Oskar
    Lund University, Malmö, Sweden.
    Cerebrospinal fluid levels of IL-6 are decreased and correlate with cognitive status in DLB patients2015In: Alzheimer's Research & Therapy, E-ISSN 1758-9193, Alzheimer's research & therapy, ISSN 1758-9193, Vol. 7, no 1, article id 63Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: Inflammatory processes have previously been shown to influence cognition and progression of dementia. An involvement of interleukin (IL)-6 has in particular been suggested as altered levels of IL-6 in cerebrospinal fluid (CSF) have been found in patients with Alzheimer's disease (AD). Also, an association between cognitive decline and levels of IL-6 in CSF have been reported. The aim of the present study was to investigate whether patients clinically diagnosed with dementia with Lewy bodies (DLB) display altered CSF IL-6 levels in comparison with patients with AD and control subjects without dementia and whether the IL-6 levels are correlated with cognitive status and biomarkers for AD and synucleinopathy.

    METHODS: To analyse CSF of patients with AD (n = 45), patients with DLB (n = 29) and control subjects without dementia (n = 36), we used immunoassays to measure levels of IL-6 (multiplex electrochemiluminescence); AD markers phosphorylated tau, total tau and amyloid-β1-42 (enzyme-linked immunosorbent assay [ELISA]); and α-synuclein (ELISA). Cognitive status was evaluated using the Mini Mental State Examination (MMSE).

    RESULTS: Our analysis showed significantly lower levels of IL-6 in CSF from patients with DLB than in CSF from patients with AD and control subjects without dementia. The IL-6 levels were also negatively correlated with MMSE and positively correlated with α-synuclein CSF levels.

    CONCLUSIONS: Our findings support previous studies by demonstrating a link between inflammatory processes and dementia progression and further strengthen the hypothesis that IL-6 is involved in dementia pathology and cognitive decline.

1 - 23 of 23
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