• Amyloid plaques and symptoms of depression links to medical help-seeking due to subjective cognitive decline 

      Espenes, Ragna; Kirsebom, Bjørn-Eivind; Eriksson, Cecilia Magdalena; Waterloo, Knut K; Hessen, Erik; Johnsen, Stein Harald; Selnes, Per; Fladby, Tormod (Journal article; Tidsskriftartikkel; Peer reviewed, 2020-06-02)
      <i>Background:</i> Subjective cognitive decline (SCD) is associated with an increased risk of Alzheimer’s disease (AD). However, patients reporting SCD to their general practitioner are not always referred to a memory clinic.<p> <p><i>Objective:</i> To investigate whether prior history of medical help-seeking is associated with AD biomarker abnormality, worse cognitive performance, and/or depressive ...
    • Association of Klotho protein levels and KL-VS heterozygosity with Alzheimer disease and amyloid and tau burden 

      Grøntvedt, Gøril Rolfseng; Sando, Sigrid Botne; Lauridsen, Camilla; Bråthen, Geir; White, Linda Rosemary; Salvesen, Øyvind; Aarsland, Dag; Hessen, Erik; Fladby, Tormod; Waterloo, Knut K; Scheffler, Katja (Journal article; Tidsskriftartikkel; Peer reviewed, 2022-11-22)
      Importance Identification of proteins and genetic factors that reduce Alzheimer disease (AD) pathology is of importance when searching for novel AD treatments. Heterozygosity of the KL-VS haplotype has been associated with reduced amyloid and tau burden. Whether this association is mediated by the Klotho protein remains unclear. Objectives To assess concentrations of Klotho in cerebrospinal ...
    • Brain amyloid and vascular risk are related to distinct white matter hyperintensity patterns 

      Pålhaugen, Lene; Sudre, Carole H; Teceläo, Sandra Raquel Ramos; Nakling, Arne; Almdahl, Ina Selseth; Kalheim, Lisa Flem; Cardoso, M Jorge; Johnsen, Stein Harald; Rongve, Arvid; Aarsland, Dag; Bjørnerud, Atle; Selnes, Per; Fladby, Tormod (Journal article; Tidsskriftartikkel; Peer reviewed, 2020-09-21)
      White matter hyperintensities (WMHs) are associated with vascular risk and Alzheimer’s disease. In this study, we examined relations between WMH load and distribution, amyloid pathology and vascular risk in 339 controls and cases with either subjective (SCD) or mild cognitive impairment (MCI). Regional deep (DWMH) and periventricular (PWMH) WMH loads were determined using an automated algorithm. We ...
    • Cerebrospinal fluid markers for synaptic function and Alzheimer type changes in late life depression 

      Siafarikas, Nikias Ioannis; Kirsebom, Bjørn-Eivind; Srivastava, Deepak P; Eriksson, Cecilia Magdalena; Auning, Eirik; Hessen, Erik; Selbæk, Geir; Blennow, Kaj; Aarsland, Dag; Fladby, Tormod (Journal article; Tidsskriftartikkel; Peer reviewed, 2021-10-13)
      To explore markers for synaptic function and Alzheimer disease (AD) pathology in late life depression (LLD), predementia AD and normal controls (NC). A cross-sectional study to compare cerebrospinal fluid (CSF) levels of neurogranin (Ng), Beta-site amyloid-precursor-protein cleaving enzyme1 (BACE1), Ng/BACE1 ratio and Amyloid-β 42/40 ratio, phosphorylated-tau and total-tau in LLD with (LLD AD) or ...
    • Cerebrospinal fluid neurofilament light chain mediates age-associated lower learning and memory in healthy adults 

      Hemminghyth, Mathilde Suhr; Chwiszczuk, Luiza; Breitve, Monica Haraldseid; Gisladottir, Berglind; Grøntvedt, Gøril Rolfseng; Nakling, Arne Exner; Rongve, Arvid; Fladby, Tormod; Kirsebom, Bjørn-Eivind Seljelid (Journal article; Tidsskriftartikkel; Peer reviewed, 2023-12-27)
      Multiple cognitive domains, including learning, memory, and psychomotor speed, show significant reductions with age. Likewise, several cerebrospinal fluid (CSF) neurodegenerative biomarkers, including total tau (t-tau, a marker of neuronal body injury) and neurofilament light chain (NfL, a marker of axonal injury) show age-related increases in normal aging. In the current study, we aimed to investigate ...
    • Cerebrospinal fluid neurogranin/β-site APP-cleaving enzyme 1 predicts cognitive decline in preclinical Alzheimer's disease 

      Kirsebom, Bjørn-Eivind; Nordengen, Kaja; Selnes, Per; Waterloo, Knut; Torsetnes, Silje Bøen; Gísladóttir, Berglind; Brix, Britta; Vanmechelen, Eugeen; Bråthen, Geir; Hessen, Erik; Aarsland, Dag; Fladby, Tormod (Journal article; Tidsskriftartikkel; Peer reviewed, 2018-11-10)
      <i>Introduction</i>: The cerebrospinal fluid neurogranin (Ng)/β-site amyloid precursor protein-cleaving enzyme 1 (BACE1) ratio may reflect synaptic affection resulting from reduced beta-amyloid (Aβ) clearance. We hypothesize that increased Ng/BACE1 ratio predicts the earliest cognitive decline in Alzheimer’s disease.<p> <p><i>Methods</i>: We compared Ng/BACE1 levels between cases with subjective ...
    • CSF, Blood, and MRI Biomarkers in Skogholt’s Disease—A Rare Neurodegenerative Disease in a Norwegian Kindred 

      Aspli, Klaus Thanke; Aaseth, Jan; Holmøy, Trygve; Blennow, Kaj; Zetterberg, Henrik; Kirsebom, Bjørn-Eivind Seljelid; Fladby, Tormod; Selnes, Per (Journal article; Tidsskriftartikkel; Peer reviewed, 2023-10-26)
      Skogholt’s disease is a rare neurological disorder that is only observed in a small Norwegian kindred. It typically manifests in adulthood with uncharacteristic neurological symptoms from both the peripheral and central nervous systems. The etiology of the observed cerebral white matter lesions and peripheral myelin pathology is unclear. Increased cerebrospinal fluid (CSF) concentrations of protein ...
    • Demographically adjusted CERAD wordlist test norms in a Norwegian sample from 40 to 80 years 

      Kirsebom, Bjørn-Eivind; Espenes, Ragna; Hessen, Erik; Waterloo, Knut; Johnsen, Stein Harald; Gundersen, Elisabeth; Sando, Sigrid Botne; Grøntvedt, Gøril Rolfseng; Timón, Santiago; Fladby, Tormod (Journal article; Tidsskriftartikkel; Peer reviewed, 2019-03-08)
      <i>Background/Objective</i>: In recent years, several slightly younger cohorts have been established in order to study the preclinical and prodromal phases of dementia. The Consortium to Establish a Registry for Alzheimer’s Disease (CERAD) wordlist memory test (WLT) is widely used in dementia research. However, culturally adapted and demographically adjusted test norms for younger ages are ...
    • Demographically adjusted Rey–Osterrieth Complex Figure Test norms in a Swedish and Norwegian cohort aged 49–77 years and comparison with North American norms 

      Öhman, Fredrik; Eckerström, Marie; Hessen, Erik; Espenes, Johan Jacob; Eliassen, Ingvild Vøllo; Lorentzen, Ingrid Myrvoll; Stålhammar, Jacob; Kettunen, Petronella; Schöll, Michael; Fladby, Tormod; Wallin, Anders; Kirsebom, Bjørn-Eivind Seljelid (Journal article; Tidsskriftartikkel; Peer reviewed, 2023-09-18)
      Introduction The Rey–Osterrieth Complex Figure Test (RCFT) is one of the most commonly used neuropsychological tests in Sweden and Norway. However, no publications provide normative data for this population. The objective of this study was to present demographically adjusted norms for a Swedish and Norwegian population and to evaluate these in an independent comparison group.<p> <p>Methods The ...
    • Demographically adjusted trail making test norms in a Scandinavian sample from 41 to 84 years 

      Espenes, Johan Jacob; Hessen, Erik; Eliassen, Ingvild Vøllo; Waterloo, Knut; Eckerström, Marie; Sando, Sigrid Botne; Timón, Santiago; Wallin, Anders; Fladby, Tormod; Kirsebom, Bjørn-Eivind (Journal article; Tidsskriftartikkel; Peer reviewed, 2020-10-09)
      <i>Objective</i> - The trail making test (TMT) is one of the most widely used neuropsychological tests. TMT-A provides measures of visual scanning/visuomotor speed and TMT-B involves additional demands on executive functions. Derived scores TMT B-A and TMT B/A enhance measures of executive functioning. However, simple B-A subtraction may lead to false estimates of executive dysfunction in clinical ...
    • Exploration of plasma lipids in mild cognitive impairment due to Alzheimer's disease 

      Bergland, Anne Katrine; Proitsi, Petroula; Kirsebom, Bjørn-Eivind; Sønnesyn, Hogne; Hye, Abdul; Larsen, Alf Inge; Xu, Jin; Legido-Quigley, Cristina; Rajendran, Lawrence; Fladby, Tormod; Aarsland, Dag (Journal article; Tidsskriftartikkel; Peer reviewed, 2020-09-29)
      <p><i>Background: </i>Lipids have important structural roles in cell membranes and changes to these membrane lipids may influence β- and γ-secretase activities and thus contribute to Alzheimer’s disease (AD) pathology. <p><i>Objective:</i> To explore baseline plasma lipid profiling in participants with mild cognitive impairment (MCI) with and without AD pathology. <p><i>Methods: </i>We identified ...
    • Genome-wide meta-analysis identifies new loci and functional pathways influencing Alzheimer's disease risk 

      Jansen, Iris E.; Savage, Jeanne E.; Watanabe, Kyoko; Bryois, Julien; Williams, Dylan M.; Steinberg, Stacy; Sealock, Julia; Karlsson, Ida K.; Hägg, Sara; Athanasiu, Lavinia; Voyle, Nicola; Proitsi, Petroula; Witoelar, Aree; Stringer, Sven; Aarsland, Dag; Almdahl, Ina Selseth; Andersen, Fred; Bergh, Sverre; Bettella, Francesco; Björnsson, Sigurbjörn; Brækhus, Anne; Bråthen, Geir; de Leeuw, Christiaan A.; Desikan, Rahul S.; Djurovic, Srdjan; Dumitrescu, Logan; Fladby, Tormod; Hohman, Timothy J.; Jónsson, Pálmi V.; Kiddle, Steven J; Rongve, Arvid; Saltvedt, Ingvild; Sando, Sigrid Botne; Selbæk, Geir; Shoai, Maryam; Skene, Nathan G.; Snædal, Jón G.; Stordal, Eystein; Ulstein, Ingun; Wang, Yunpeng; White, Linda Rosemary; Hardy, John; Hjerling-Leffler, Jens; Sullivan, Patrick; van der Flier, Wiesje M.; Dobson, Richard; Davis, Lea K; Stefánsson, Hreinn; Stefánsson, Kári; Pedersen, Nancy L; Ripke, Stephan; Andreassen, Ole Andreas; Posthuma, Danielle (Journal article; Tidsskriftartikkel; Peer reviewed, 2019-01-07)
      Alzheimer’s disease (AD) is highly heritable and recent studies have identified over 20 disease-associated genomic loci. Yet these only explain a small proportion of the genetic variance, indicating that undiscovered loci remain. Here, we performed a large genome-wide association study of clinically diagnosed AD and AD-by-proxy (71,880 cases, 383,378 controls). AD-by-proxy, based on parental diagnoses, ...
    • Glial activation and inflammation along the Alzheimer's disease continuum 

      Nordengen, Kaja; Kirsebom, Bjørn-Eivind; Henjum, Kristi; Selnes, Per; Gisladottir, Berglind; Wettergreen, Marianne; Torsetnes, Silje Bøen; Grøntvedt, Gøril Rolfseng; Waterloo, Knut; Aarsland, Dag; Nilsson, Lars; Fladby, Tormod (Journal article; Tidsskriftartikkel; Peer reviewed, 2019-02-21)
      <p><i>Background - </i>Neuronal and glial cell interaction is essential for synaptic homeostasis and may be affected in Alzheimer’s disease (AD). We measured cerebrospinal fluid (CSF) neuronal and glia markers along the AD continuum, to reveal putative protective or harmful stage-dependent patterns of activation. <p><i>Methods - </i>We included healthy controls (<i>n</i> = 36) and Aβ-positive (Aβ+) ...
    • Improving validity of the trail making test with alphabet support 

      Waggestad, Therese Händel; Kirsebom, Bjørn-Eivind; Strobel, Carsten; Wallin, Anders; Eckerström, Marie; Fladby, Tormod; Egeland, Jens (Journal article; Tidsskriftartikkel; Peer reviewed, 2023-07-27)
      The Trail Making Test (TMT) is commonly used worldwide to evaluate cognitive decline and car driving ability. However, it has received critique for its dependence on the Latin alphabet and thus, the risk of misclassifying some participants. Alphabet support potentially increases test validity by avoiding misclassification of executive dysfunction in participants with dyslexia and those with insufficient ...
    • In Brief Neuropsychological Assessment, Amnestic Mild Cognitive Impairment (MCI) Is associated with Cerebrospinal Fluid Biomarkers for Cognitive Decline in Contrast to the Prevailing NIA-AA MCI Criterion 

      Hessen, Erik; Kirsebom, Bjørn-Eivind; Eriksson, Cecilia Magdalena; Eliassen, Carl Fredrik Andestad; Nakling, Arne; Bråthen, Geir; Waterloo, Knut; Aarsland, Dag; Fladby, Tormod (Journal article; Tidsskriftartikkel; Peer reviewed, 2019-01-22)
      <i>Background:</i> In the care of persons with cognitive problems, it is important to use a valid mild cognitive impairment (MCI) criterion that discriminates well between normal and pathological aging.<p> <p><i>Objective:</i> To find the brief neuropsychological screening criterion that best correlates with cerebrospinal fluid (CSF) biomarkers for cognitive decline and dementia in persons ...
    • Investigating the relationship between allocentric spatial working memory and biomarker status in preclinical and prodromal Alzheimer’s disease. 

      Lorentzen, Ingrid Myrvoll; Espenes, Johan Jacob; Eliassen, Ingvild Vøllo; Hessen, Erik; Waterloo, Knut K; Nakling, Arne Exner; Gisladottir, Berglind; Jarholm, Jonas Alexander; Fladby, Tormod; Kirsebom, Bjørn-Eivind (Journal article; Tidsskriftartikkel; Peer reviewed, 2023-08-08)
      The 4 Mountain Test (4MT) is a test of allocentric spatial working memory and has been proposed as an earlier marker of predementia Alzheimer’s disease (AD) than episodic verbal memory. We here compare the 4MT to the CERAD word list memory recall in both cognitively normal (CN) and mild cognitive impairment (MCI) cases with or without cerebrospinal fluid markers (CSF) of Alzheimer’s disease ...
    • A Knowledge Graph Framework for Dementia Research Data 

      Timón, Santiago; Rincón, Mariano; Martínez-Tomás, Rafael; Kirsebom, Bjørn-Eivind Seljelid; Fladby, Tormod (Journal article; Tidsskriftartikkel; Peer reviewed, 2023-09-20)
      Dementia disease research encompasses diverse data modalities, including advanced imaging, deep phenotyping, and multi-omics analysis. However, integrating these disparate data sources has historically posed a significant challenge, obstructing the unification and comprehensive analysis of collected information. In recent years, knowledge graphs have emerged as a powerful tool to address such ...
    • Longitudinal cerebrospinal fluid measurements show glial hypo- and hyperactivation in predementia Alzheimer’s disease 

      Nordengen, Kaja; Kirsebom, Bjørn-Eivind Seljelid; Richter, Grit; Pålhaugen, Lene; Gisladottir, Berglind; Siafarikas, Nikias Ioannis; Nakling, Arne Exner; Rongve, Arvid; Bråthen, Geir; Grøntvedt, Gøril Rolfseng; Gonzalez, Fernando; Waterloo, Knut; Sharma, Kulbhushan; Karikari, Thomas; Vromen, Eleonora M.; Tijms, Betty M.; Visser, Pieter J.; Selnes, Per; Kramberger, Milicia G.; Winblad, Bengt; Blennow, Kaj; Fladby, Tormod (Journal article; Tidsskriftartikkel; Peer reviewed, 2023-12-13)
      Background - Brain innate immune activation is associated with Alzheimer’s disease (AD), but degrees of activation may vary between disease stages. Thus, brain innate immune activation must be assessed in longitudinal clinical studies that include biomarker negative healthy controls and cases with established AD pathology. Here, we employ longitudinally sampled cerebrospinal fluid (CSF) core AD, ...
    • Medial Temporal Lobe Atrophy in Predementia Alzheimer's Disease: A Longitudinal Multi-Site Study Comparing Staging and A/T/N in a Clinical Research Cohort 

      Jarholm, Jonas Alexander; Bjørnerud, Atle; Dalaker, Turi Olene; Akhavi, Mehdi Sadat; Kirsebom, Bjørn-Eivind; Pålhaugen, Lene; Nordengen, Kaja; Grøntvedt, Gøril Rolfseng; Nakling, Arne Exner; Kalheim, Lisa Flem; Almdahl, Ina Selseth; Teceläo, Sandra Raquel Ramos; Fladby, Tormod; Selnes, Per (Journal article; Tidsskriftartikkel; Peer reviewed, 2023-06-27)
      Background: Atrophy of the medial temporal lobe (MTL) is a biological characteristic of Alzheimer’s disease (AD) and can be measured by segmentation of magnetic resonance images (MRI). Objective: To assess the clinical utility of automated volumetry in a cognitively well-defined and biomarker-classified multi-center longitudinal predementia cohort. <p>Methods: We used Automatic Segmentation of ...
    • Meta-analysis of Alzheimer’s disease on 9,751 samples from Norway and IGAP study identifies four risk loci 

      Witoelar, Aree; Rongve, Arvid; Almdahl, Ina Selseth; Ulstein, Ingun; Engvig, Andreas; White, Linda Rosemary; Selbæk, Geir; Stordal, Eystein; Andersen, Fredrik; Brækhus, Anne; Saltvedt, Ingvild; Engedal, Knut; Hughes, Timothy; Bergh, Sverre; Bråthen, Geir; Bogdanovic, Nenad; Bettella, Francesco; Wang, Yunpeng; Athanasiu, Lavinia; Bahrami, Shahram; Le Hellard, Stephanie; Giddaluru, Sudheer; Dale, Anders M; Sando, Sigrid Botne; Steinberg, Stacy; Stefansson, Hreinn; Snaedal, Jon; Desikan, Rahul S; Stefansson, Kari; Aarsland, Dag; Djurovic, Srdjan; Fladby, Tormod; Andreassen, Ole Andreas (Journal article; Tidsskriftartikkel; Peer reviewed, 2018-12-27)
      A large fraction of genetic risk factors for Alzheimer’s Disease (AD) is still not identified, limiting the understanding of AD pathology and study of therapeutic targets. We conducted a genome-wide association study (GWAS) of AD cases and controls of European descent from the multi-center DemGene network across Norway and two independent European cohorts. In a two-stage process, we first performed ...