SwePub
Sök i SwePub databas

  Extended search

Träfflista för sökning "WFRF:(Aarsland Dag) "

Search: WFRF:(Aarsland Dag)

  • Result 1-50 of 71
Sort/group result
   
EnumerationReferenceCoverFind
1.
  • Abdelnour, Carla, et al. (author)
  • Parsing heterogeneity within dementia with Lewy bodies using clustering of biological, clinical, and demographic data
  • 2022
  • In: Alzheimer's Research & Therapy. - : Springer Science and Business Media LLC. - 1758-9193. ; 14:1
  • Journal article (peer-reviewed)abstract
    • Background: Dementia with Lewy bodies (DLB) includes various core clinical features that result in different phenotypes. In addition, Alzheimer's disease (AD) and cerebrovascular pathologies are common in DLB. All this increases the heterogeneity within DLB and hampers clinical diagnosis. We addressed this heterogeneity by investigating subgroups of patients with similar biological, clinical, and demographic features.Methods: We studied 107 extensively phenotyped DLB patients from the European DLB consortium. Factorial analysis of mixed data (FAMD) was used to identify dimensions in the data, based on sex, age, years of education, disease duration, Mini-Mental State Examination (MMSE), cerebrospinal fluid (CSF) levels of AD biomarkers, core features of DLB, and regional brain atrophy. Subsequently, hierarchical clustering analysis was used to subgroup individuals based on the FAMD dimensions.Results: We identified 3 dimensions using FAMD that explained 38% of the variance. Subsequent hierarchical clustering identified 4 clusters. Cluster 1 was characterized by amyloid-beta and cerebrovascular pathologies, medial temporal atrophy, and cognitive fluctuations. Cluster 2 had posterior atrophy and showed the lowest frequency of visual hallucinations and cognitive fluctuations and the worst cognitive performance. Cluster 3 had the highest frequency of tau pathology, showed posterior atrophy, and had a low frequency of parkinsonism. Cluster 4 had virtually normal AD biomarkers, the least regional brain atrophy and cerebrovascular pathology, and the highest MMSE scores.Conclusions: This study demonstrates that there are subgroups of DLB patients with different biological, clinical, and demographic characteristics. These findings may have implications in the diagnosis and prognosis of DLB, as well as in the treatment response in clinical trials.
  •  
2.
  • Alves, Guido, et al. (author)
  • Cerebrospinal fluid amyloid-β and phenotypic heterogeneity in de novo Parkinson's disease.
  • 2013
  • In: Journal of neurology, neurosurgery, and psychiatry. - : BMJ. - 1468-330X .- 0022-3050. ; 84:5, s. 537-43
  • Journal article (peer-reviewed)abstract
    • In Parkinson's disease (PD), the motor presentation characterised by postural instability/gait difficulties (PIGD) heralds accelerated motor, functional and cognitive decline, as compared with the more benign tremor-dominant (TD) variant. This makes the PIGD complex an attractive target for the discovery of prognostic biomarkers in PD.
  •  
3.
  • Alves, Guido, et al. (author)
  • CSF amyloid-β and tau proteins, and cognitive performance, in early and untreated Parkinson's Disease: the Norwegian ParkWest study
  • 2010
  • In: Journal of neurology, neurosurgery, and psychiatry. - : BMJ. - 1468-330X .- 0022-3050. ; 81:10, s. 1080-1086
  • Journal article (peer-reviewed)abstract
    • Background Alzheimer's disease (AD) pathology is found in a considerable portion of patients with Parkinson's disease (PD), particularly those with early dementia (PDD). Altered cerebrospinal fluid (CSF) levels of amyloid-beta (Abeta) and tau proteins have been found in PDD, with intermediate changes for Abeta42 in non-demented PD. The authors investigated whether AD-related CSF protein levels are altered and relate to neuropsychological performance in early, untreated PD. Methods CSF concentrations of Abeta42, Abeta40 and Abeta38 were measured by electrochemiluminiscene and levels of total tau (T-tau) and phosphorylated tau (P-tau) by ELISA in 109 newly diagnosed, unmedicated, non-demented, community-based PD patients who had undergone comprehensive neuropsychological testing, and were compared with those of 36 age-matched normal controls and 20 subjects with mild AD. Results PD patients displayed significant reductions in Abeta42 (19%; p=0.009), Abeta40 (15.5%; p=0.008) and Abeta38 (23%; p=0.004) but not T-tau (p=0.816) or P-tau (p=0.531) compared with controls. CSF Abeta42 reductions in PD were less marked than in AD (53%; p=0.002). Sequential regression analyses demonstrated significant associations between CSF levels of Abeta42 (beta=0.205; p=0.019), Abeta40 (beta=0.378; p<0.001) and Abeta38 (beta=0.288; p=0.001) and memory impairment, but not executive-attentional or visuospatial dysfunction. Tau protein levels did not correlate with cognitive measures. Conclusion CSF Abeta levels are altered in a subset of patients with early PD and relate to memory impairment. Our study suggests that alterations in Abeta protein metabolism may contribute to the heterogeneity in pattern and course of cognitive decline associated with PD. Longitudinal studies are needed to clarify the clinical significance of CSF Abeta peptides as prognostic biomarkers in PD.
  •  
4.
  • Ashton, Nicholas J., et al. (author)
  • A multicentre validation study of the diagnostic value of plasma neurofilament light
  • 2021
  • In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12, s. 1-12
  • Journal article (peer-reviewed)abstract
    • Increased cerebrospinal fluid neurofilament light (NfL) is a recognized biomarker for neurodegeneration that can also be assessed in blood. Here, we investigate plasma NfL as a marker of neurodegeneration in 13 neurodegenerative disorders, Down syndrome, depression and cognitively unimpaired controls from two multicenter cohorts: King's College London (n = 805) and the Swedish BioFINDER study (n = 1,464). Plasma NfL was significantly increased in all cortical neurodegenerative disorders, amyotrophic lateral sclerosis and atypical parkinsonian disorders. We demonstrate that plasma NfL is clinically useful in identifying atypical parkinsonian disorders in patients with parkinsonism, dementia in individuals with Down syndrome, dementia among psychiatric disorders, and frontotemporal dementia in patients with cognitive impairment. Data-driven cut-offs highlighted the fundamental importance of age-related clinical cut-offs for disorders with a younger age of onset. Finally, plasma NfL performs best when applied to indicate no underlying neurodegeneration, with low false positives, in all age-related cut-offs.
  •  
5.
  • Ashton, Nicholas J., et al. (author)
  • A plasma protein classifier for predicting amyloid burden for preclinical Alzheimer's disease.
  • 2019
  • In: Science advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 5:2
  • Journal article (peer-reviewed)abstract
    • A blood-based assessment of preclinical disease would have huge potential in the enrichment of participants for Alzheimer's disease (AD) therapeutic trials. In this study, cognitively unimpaired individuals from the AIBL and KARVIAH cohorts were defined as Aβ negative or Aβ positive by positron emission tomography. Nontargeted proteomic analysis that incorporated peptide fractionation and high-resolution mass spectrometry quantified relative protein abundances in plasma samples from all participants. A protein classifier model was trained to predict Aβ-positive participants using feature selection and machine learning in AIBL and independently assessed in KARVIAH. A 12-feature model for predicting Aβ-positive participants was established and demonstrated high accuracy (testing area under the receiver operator characteristic curve = 0.891, sensitivity = 0.78, and specificity = 0.77). This extensive plasma proteomic study has unbiasedly highlighted putative and novel candidates for AD pathology that should be further validated with automated methodologies.
  •  
6.
  • Ashton, Nicholas J., et al. (author)
  • An update on blood-based biomarkers for non-Alzheimer neurodegenerative disorders.
  • 2020
  • In: Nature Reviews Neurology. - : Springer Science and Business Media LLC. - 1759-4766 .- 1759-4758. ; 16, s. 265-284
  • Research review (peer-reviewed)abstract
    • Cerebrospinal fluid analyses and neuroimaging can identify the underlying pathophysiology at the earliest stage of some neurodegenerative disorders, but do not have the scalability needed for population screening. Therefore, a blood-based marker for such pathophysiology would have greater utility in a primary care setting and in eligibility screening for clinical trials. Rapid advances in ultra-sensitive assays have enabled the levels of pathological proteins to be measured in blood samples, but research has been predominantly focused on Alzheimer disease (AD). Nonetheless, proteins that were identified as potential blood-based biomarkers for AD, for example, amyloid-β, tau, phosphorylated tau and neurofilament light chain, are likely to be relevant to other neurodegenerative disorders that involve similar pathological processes and could also be useful for the differential diagnosis of clinical symptoms. This Review outlines the neuropathological, clinical, molecular imaging and cerebrospinal fluid features of the most common neurodegenerative disorders outside the AD continuum and gives an overview of the current status of blood-based biomarkers for these disorders.
  •  
7.
  • Ashton, Nicholas J., et al. (author)
  • Increased plasma neurofilament light chain concentration correlates with severity of post-mortem neurofibrillary tangle pathology and neurodegeneration
  • 2019
  • In: Acta Neuropathologica Communications. - : Springer Science and Business Media LLC. - 2051-5960. ; 7:1
  • Journal article (peer-reviewed)abstract
    • Alzheimer's disease (AD) is pathologically characterized by the accumulation of amyloid-β (Aβ) plaques, neurofibrillary tangles and widespread neuronal loss in the brain. In recent years, blood biomarkers have emerged as a realistic prospect to highlight accumulating pathology for secondary prevention trials. Neurofilament light chain (NfL), a marker of axonal degeneration, is robustly elevated in the blood of many neurological and neurodegenerative conditions, including AD. A strong relationship with cerebrospinal fluid (CSF) NfL suggests that these biomarker modalities reflect the same pathological process. Yet, the connection between blood NfL and brain tissue pathology has not been directly compared. In this study, longitudinal plasma NfL from cognitively healthy controls (n = 12) and AD participants (n = 57) were quantified by the Simoa platform. On reaching post-mortem, neuropathological assessment was performed on all participants, with additional frozen and paraffin-embedded tissue acquired from 26 participants for further biochemical (Aβ1-42, Aβ1-40, tau) and histological (NfL) evaluation. Plasma NfL concentrations were significantly increased in AD and correlated with cognitive decline, independent of age. Retrospective stratification based on Braak staging revealed that baseline plasma NfL concentrations were associated with higher neurofibrillary tangle pathology at post-mortem. Longitudinal increases in plasma NfL were observed in all Braak groupings; a significant negative association, however, was found between plasma NfL at time point 1 and both its rate of change and annual percentage increase. Immunohistochemical evaluation of NfL in the medial temporal gyrus (MTG) demonstrated an inverse relationship between Braak stages and NfL staining. Importantly, a significant negative correlation was found between the plasma NfL measurement closest to death and the level of NfL staining in the MTG at post-mortem. For the first time, we demonstrate that plasma NfL associates with the severity of neurofibrillary tangle pathology and neurodegeneration in the post-mortem brain.
  •  
8.
  • Ballard, Clive, et al. (author)
  • alpha-synuclein antibodies recognize a protein present at lower levels in the CSF of patients with dementia with Lewy bodies
  • 2010
  • In: International Psychogeriatrics. - 1741-203X. ; 22:2, s. 321-327
  • Journal article (peer-reviewed)abstract
    • Background: Dementia with Lewy bodies (DLB) accounts for 15-20%, of the millions of people worldwide with dementia. Accurate diagnosis is essential to avoid harm and optimize clinical management. There is therefore an urgent need to identify reliable biomarkers. Methods: Mass spectrometry was used to determine the specificity of antibody alpha-synuclein (211) for alpha-synuclein. Using gel electrophoresis we measured protein levels detected by alpha-synuclein specific antibodies in the cerebrospinal fluid (CSF) of DLB patients and compared them to age matched controls. Results: A 24 kDa band was detected using alpha-synuclein specific antibodies which was significantly reduced in the CSF of DLB patients compared to age matched controls (p < 0.05). Further analysis confirmed that even DLB patients with mild dementia showed significant reductions in this protein in comparison to controls. Conclusions: The current study emphasizes the necessity for further studies of CSF alpha-synuclein as a biomarker of DLB and extends our previous knowledge by establishing a potential relationship between alpha-synuclein and the severity of cognitive impairment. The identification of this 24 kDa protein is the next important step in these studies.
  •  
9.
  • Batzu, Lucia, et al. (author)
  • Plasma p-tau181, neurofilament light chain and association with cognition in Parkinson's disease.
  • 2022
  • In: NPJ Parkinson's disease. - : Springer Science and Business Media LLC. - 2373-8057. ; 8:1
  • Journal article (peer-reviewed)abstract
    • Early identification of cognitive impairment in Parkinson's disease (PD) has important clinical and research implications. The aim of our study was to investigate the role of plasma tau phosphorylated at amino acid 181 (p-tau181) and plasma neurofilament light chain (NfL) as biomarkers of cognition in PD. Baseline concentrations of plasma p-tau181 and NfL were measured in a cohort of 136 patients with PD and 63 healthy controls (HC). Forty-seven PD patients were followed up for up to 2 years. Cross-sectional and longitudinal associations between baseline plasma biomarkers and cognitive progression were investigated using linear regression and linear mixed effects models. At baseline, plasma p-tau181 concentration was significantly higher in PD subjects compared with HC (p=0.026). In PD patients, higher plasma NfL was associated with lower MMSE score at baseline, after adjusting for age, sex and education (p=0.027). Baseline plasma NfL also predicted MMSE decline over time in the PD group (p=0.020). No significant association between plasma p-tau181 concentration and baseline or longitudinal cognitive performance was found. While the role of p-tau181 as a diagnostic biomarker for PD and its relationship with cognition need further elucidation, plasma NfL may serve as a feasible, non-invasive biomarker of cognitive progression in PD.
  •  
10.
  • Bauckneht, Matteo, et al. (author)
  • Associations among education, age, and the dementia with Lewy bodies (DLB) metabolic pattern: A European-DLB consortium project
  • 2021
  • In: Alzheimer's & Dementia. - : WILEY. - 1552-5260 .- 1552-5279. ; 17:8, s. 1277-1286
  • Journal article (peer-reviewed)abstract
    • Introduction We assessed the influence of education as a proxy of cognitive reserve and age on the dementia with Lewy bodies (DLB) metabolic pattern. Methods Brain 18F-fluorodeoxyglucose positron emission tomography and clinical/demographic information were available in 169 probable DLB patients included in the European DLB-consortium database. Principal component analysis identified brain regions relevant to local data variance. A linear regression model was applied to generate age- and education-sensitive maps corrected for Mini-Mental State Examination score, sex (and either education or age). Results Age negatively covaried with metabolism in bilateral middle and superior frontal cortex, anterior and posterior cingulate, reducing the expression of the DLB-typical cingulate island sign (CIS). Education negatively covaried with metabolism in the left inferior parietal cortex and precuneus (making the CIS more prominent). Discussion These findings point out the importance of tailoring interpretation of DLB biomarkers considering the concomitant effect of individual, non-disease-related variables such as age and cognitive reserve.
  •  
11.
  • Bloniecki, Victor, et al. (author)
  • Agitation in dementia : relation to core cerebrospinal fluid biomarker levels
  • 2014
  • In: Dementia and Geriatric Cognitive Disorders Extra. - : S. Karger. - 1664-5464. ; 4:2, s. 335-43
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: The objective of this study was to examine the associations of agitation with the cerebrospinal fluid dementia biomarkers total-tau (T-tau), phosphorylated-tau (P-tau) and Aβ1-42.METHODS: One hundred patients (mean age ± SD, 78.6 ± 7.5 years) with dementia and neuropsychiatric symptoms, of whom 67% were female, were included. Agitation was measured using the Cohen-Mansfield Agitation Inventory (CMAI; 46.5 ± 11.8 points).RESULTS: Total CMAI correlated with T-tau [rs (31) = 0.36, p = 0.04] and P-tau [rs (31) = 0.35, p = 0.05] in patients with Alzheimer's disease (AD; n = 33) but not in the total dementia population (n = 95).CONCLUSIONS: Our results suggest that tau-mediated pathology including neurofibrillary tangles and the intensity of the disease process might be associated with agitation in AD.
  •  
12.
  • Bloniecki, Victor, et al. (author)
  • Are neuropsychiatric symptoms in dementia linked to CSF biomarkers of synaptic and axonal degeneration?
  • 2020
  • In: Alzheimer's Research & Therapy. - : BioMed Central. - 1758-9193. ; 12:1
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: The underlying disease mechanism of neuropsychiatric symptoms (NPS) in dementia remains unclear. Cerebrospinal fluid (CSF) biomarkers for synaptic and axonal degeneration may provide novel neuropathological information for their occurrence. The aim was to investigate the relationship between NPS and CSF biomarkers for synaptic (neurogranin [Ng], growth-associated protein 43 [GAP-43]) and axonal (neurofilament light [NFL]) injury in patients with dementia.METHODS: A total of 151 patients (mean age ± SD, 73.5 ± 11.0, females n = 92 [61%]) were included, of which 64 had Alzheimer's disease (AD) (34 with high NPS, i.e., Neuropsychiatric Inventory (NPI) score > 10 and 30 with low levels of NPS) and 18 were diagnosed with vascular dementia (VaD), 27 with mixed dementia (MIX), 12 with mild cognitive impairment (MCI), and 30 with subjective cognitive impairment (SCI). NPS were primarily assessed using the NPI. CSF samples were analyzed using enzyme-linked immunosorbent assays (ELISAs) for T-tau, P-tau, Aβ1-42, Ng, NFL, and GAP-43.RESULTS: No significant differences were seen in the CSF levels of Ng, GAP-43, and NFL between AD patients with high vs low levels of NPS (but almost significantly decreased for Ng in AD patients < 70 years with high NPS, p = 0.06). No significant associations between NPS and CSF biomarkers were seen in AD patients. In VaD (n = 17), negative correlations were found between GAP-43, Ng, NFL, and NPS.CONCLUSION: Our results could suggest that low levels of Ng may be associated with higher severity of NPS early in the AD continuum (age < 70). Furthermore, our data may indicate a potential relationship between the presence of NPS and synaptic as well as axonal degeneration in the setting of VaD pathology.
  •  
13.
  • Bloniecki, Victor, et al. (author)
  • Effects of Risperidone and Galantamine Treatment on Alzheimer's Disease Biomarker Levels in Cerebrospinal Fluid
  • 2017
  • In: Journal of Alzheimer's Disease. - : IOS Press. - 1387-2877 .- 1875-8908. ; 57:2, s. 387-393
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Treatment for neuropsychiatric symptoms (NPS) in dementia is insufficient. Antipsychotics and acetylcholinesterase inhibitors are used generating symptomatic improvements in behavior and cognition, but few studies have investigated their effect on Alzheimer's disease (AD) biomarkers in cerebrospinal fluid (CSF).OBJECTIVE: This is a secondary analysis based on an earlier clinical trial comparing the treatment effects on NPS. The aim of this study was to examine whether treatment with risperidone and galantamine affect levels of the biomarkers T-Tau, P-Tau, Aβ1-42, and Aβ42/40-ratio in CSF. The secondary aim was to test if baseline levels of these biomarkers are associated with the clinical course of NPS.METHODS: 83 patients (mean + SD 77.9.6±7.7 years) with dementia and NPS were randomized to galantamine (n = 44) or risperidone (n = 39) treatment. CSF samples were collected at baseline and after 12 weeks.RESULTS: Changes in levels of biomarkers between the two treatment groups did not differ significantly. Low baseline levels of Aβ1 - 42 was significantly associated with reduction of irritability at follow up. Low baseline levels of Aβ1-42, Aβ42/40, and P-Tau were significant correlates of reduction in appetite and eating disorders. CSF Aβ1-42 levels in patients treated with risperidone were significantly decreased at follow up, showing an 8% (40 pg/mL) reduction as compared with baseline (p = 0.03).CONCLUSIONS: Our results suggest that risperidone may affect the CSF profile of AD biomarkers indicating more amyloid pathology. Treatment with galantamine did not affect the CSF biomarkers in any direction. The AD CSF biomarkers displayed correlations with specific NPS suggesting potential research questions to be pursued.
  •  
14.
  • Borda, Miguel German, et al. (author)
  • Nutrient Intake and Its Association with Appendicular Total Lean Mass and Muscle Function and Strength in Older Adults: A Population-Based Study
  • 2024
  • In: NUTRIENTS. - : MDPI. - 2072-6643. ; 16:4
  • Journal article (peer-reviewed)abstract
    • Treatment options for sarcopenia are currently limited, and primarily rely on two main therapeutic approaches: resistance-based physical activity and dietary interventions. However, details about specific nutrients in the diet or supplementation are unclear. We aim to investigate the relationship between nutrient intake and lean mass, function, and strength. Data were derived from the Gothenburg H70 birth cohort study in Sweden, including 719,70-year-olds born in 1944 (54.1% females). For independent variables, the diet history method (face-to-face interviews) was used to estimate habitual food intake during the preceding three months. Dependent variables were gait speed (muscle performance), hand grip strength (muscle strength), and the appendicular lean soft tissue index (ALSTI). Linear regression analyses were performed to analyze the relationship between the dependent variables and each of the covariates. Several nutrients were positively associated with ALSTI, such as polyunsaturated fatty acids (DHA, EPA), selenium, zinc, riboflavin, niacin equivalent, vitamin B12, vitamin D, iron, and protein. After correction for multiple comparisons, there were no remaining correlations with handgrip and gait speed. Findings of positive correlations for some nutrients with lean mass suggest a role for these nutrients in maintaining muscle volume. These results can be used to inform clinical trials to expand the preventive strategies and treatment options for individuals at risk of muscle loss and sarcopenia.
  •  
15.
  • Borda, Miguel German, et al. (author)
  • Temporal Muscle Thickness: A Practical Approximation for Assessing Muscle Mass in Older Adults
  • 2024
  • In: JOURNAL OF THE AMERICAN MEDICAL DIRECTORS ASSOCIATION. - 1525-8610 .- 1538-9375. ; 25:4
  • Journal article (peer-reviewed)abstract
    • Objective: Ongoing research has evidenced the importance of muscle measurement in predicting adverse outcomes. Measurement of other muscles is promising in current research. This study aimed to determine the correlation between temporal muscle thickness (TMT) and appendicular lean soft tissue (ALSTI) in older adults. Design: Cross-sectional study. Settings and Participants: Single cohort gathered in Gothenburg, Sweden, consisting of individuals born in 1944 (n = 1203). Methods: We studied 657 magnetic resonance images to measure TMT. Comparisons of TMT with dual -energy X-ray absorptiometry ALSTI (kg/m 2 ) as a reference standard were performed. Finally, TMT associations with cognition evaluated using the Mini -Mental State Examination (MMSE), gait speed, and handgrip strength were explored with linear regressions. Results: The correlation between TMT and ALSTI was weak yet signi ficant (r = 0.277, P < .001). TMT exhibited signi ficant associations with MMSE (estimate = 0.168, P = .002), gait speed (estimate =1.795, P < .001), and ALSTI (estimate = 0.508, P < .001). These associations varied when analyzed by sex. In women, TMT was signi ficantly associated with gait speed (estimate = 1.857, P = .005) and MMSE (estimate = 0.223, P = .003). In men, TMT scores were signi ficantly correlated with ALSTI scores (estimate = 0.571, P < .001). Conclusion and Implications: Repurposing head images can be an accessible alternative to detect muscle mass and ultimately detect sarcopenia. These studies have the potential to trigger interventions or further evaluation to improve the muscle and overall health of individuals. However, additional research is warranted before translating these findings into clinical practice. (c) 2024 AMDA - The Society for Post -Acute and Long -Term Care Medicine.
  •  
16.
  • Borda, Miguel German, et al. (author)
  • Using magnetic resonance imaging to measure head muscles: An innovative method to opportunistically determine muscle mass and detect sarcopenia
  • 2024
  • In: Journal of Cachexia, Sarcopenia and Muscle. - 2190-5991 .- 2190-6009. ; 15:1, s. 189-197
  • Journal article (peer-reviewed)abstract
    • Background: Sarcopenia is associated with multiple adverse outcomes. Traditional methods to determine low muscle mass for the diagnosis of sarcopenia are mainly based on dual-energy X-ray absorptiometry (DXA), whole-body magnetic resonance imaging (MRI) and bioelectrical impedance analysis. These tests are not always available and are rather time consuming and expensive. However, many brain and head diseases require a head MRI. In this study, we aim to provide a more accessible way to detect sarcopenia by comparing the traditional method of DXA lean mass estimation versus the tongue and masseter muscle mass assessed in a standard brain MRI. Methods: The H70 study is a longitudinal study of older people living in Gothenburg, Sweden. In this cross-sectional analysis, from 1203 participants aged 70years at baseline, we included 495 with clinical data and MRI images available. We used the appendicular lean soft tissue index (ALSTI) in DXA images as our reference measure of lean mass. Images from the masseter and tongue were analysed and segmented using 3D Slicer. For the statistical analysis, the Spearman correlation coefficient was used, and concordance was estimated with the Kappa coefficient. Results: The final sample consisted of 495 participants, of which 52.3% were females. We found a significant correlation coefficient between both tongue (0.26) and masseter (0.33) with ALSTI (P<0.001). The sarcopenia prevalence confirmed using the alternative muscle measure in MRI was calculated using the ALSTI (tongue=2.0%, masseter=2.2%, ALSTI=2.4%). Concordance between sarcopenia with masseter and tongue versus sarcopenia with ALSTI as reference has a Kappa of 0.989 (P<0.001) for masseter and a Kappa of 1 for the tongue muscle (P<0.001). Comorbidities evaluated with the Cumulative Illness Rating Scale were significantly associated with all the muscle measurements: ALSTI (odds ratio [OR] 1.16, 95% confidence interval [CI] 1.07–1.26, P<0.001), masseter (OR 1.16, 95% CI 1.07–1.26, P<0.001) and tongue (OR 1.13, 95% CI 1.04–1.22, P=0.002); the higher the comorbidities, the higher the probability of having abnormal muscle mass. Conclusions: ALSTI was significantly correlated with tongue and masseter muscle mass. When performing the sarcopenia diagnostic algorithm, the prevalence of sarcopenia calculated with head muscles did not differ from sarcopenia calculated using DXA, and almost all participants were correctly classified using both methods.
  •  
17.
  • Creese, Byron, et al. (author)
  • Determining the Association of the 5HTTLPR Polymorphism with Delusions and Hallucinations in Lewy Body Dementias
  • 2014
  • In: The American Journal of Geriatric Psychiatry. - : Elsevier BV. - 1545-7214 .- 1064-7481. ; 22:6, s. 580-586
  • Journal article (peer-reviewed)abstract
    • Objectives: To determine whether the 5HTTLPR serotonin transporter polymorphism is associated with delusions and hallucinations in people with dementia with Lewy bodies (DLB) and Parkinson disease dementia (PDD). Design: Prospective cohort study. Participants: A total of 187 individuals, recruited from centres in Norway, Sweden, and the United Kingdom were included in this study; 97 with clinically or neuropathologically diagnosed DLB/PDD and 90 cognitively normal individuals as a comparison group. Measurements: All participants with dementia underwent serial evaluation of neuropsychiatric symptoms to assess the presence of persistent delusions and hallucinations using the Columbia University Scale for Psychopathology in Alzheimer disease, the Neuropsychiatric Inventory, or the Present Behavioural Examination. Severity of cognitive impairment was measured using the Mini Mental State Examination (MMSE). Individuals were genotyped for the 5HTTLPR polymorphism. Results: Logistic regression demonstrated that homozygosity for the L/L genotype and lower MMSE were associated with an increased risk for delusions (odds ratio: 11.5 and 1.16, respectively). Neither was significantly associated with hallucinations. Conclusions: This study is the first to demonstrate the 5HTTLPR polymorphism is associated with delusions in Lewy body dementias, with important implications regarding the mechanisms underlying this symptom across the AD/DLB/PDD spectrum. Further studies are warranted to investigate this relationship further and examine treatment opportunities.
  •  
18.
  • Creese, Byron, et al. (author)
  • No association of COMT val158met polymorphism and psychotic symptoms in Lewy body dementias
  • 2012
  • In: Neuroscience Letters. - : Elsevier BV. - 0304-3940 .- 1872-7972. ; 531:1, s. 1-4
  • Journal article (peer-reviewed)abstract
    • We sought to determine whether the COMT val158met polymorphism (rs4680) is associated with delusions and hallucinations in people with dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD). A total of 218 individuals, recruited from centres in Norway, Sweden and the UK were included in this study; 121 with clinically or neuropathologically diagnosed DLB/PDD and 97 age-matched, cognitively normal controls. All participants with dementia underwent serial evaluation of neuropsychiatric symptoms to assess the presence of persistent delusions and hallucinations using the Columbia University Scale for Psychopathology in Alzheimer's disease, the Neuropsychiatric Inventory or the Present Behavioural Examination. Severity of cognitive impairment was measured using the Mini Mental State Examination (MMSE). Both controls and participants with dementia were genotyped for rs4680. In contrast to previous findings, analysis by logistic regression failed to find any associations between rs4680 and psychotic symptoms. Larger studies in well characterised cohorts are warranted in order to investigate this relationship further. (C) 2012 Elsevier Ireland Ltd. All rights reserved.
  •  
19.
  • Damangir, Soheil, et al. (author)
  • Multispectral MRI segmentation of age related white matter changes using a cascade of support vector machines
  • 2012
  • In: Journal of the Neurological Sciences. - : Elsevier BV. - 0022-510X .- 1878-5883. ; 322:1-2, s. 211-216
  • Journal article (peer-reviewed)abstract
    • White matter changes (WMC) are the focus of intensive research and have been linked to cognitive impairment and depression in the elderly. Cumbersome manual outlining procedures make research on WMC labor intensive and prone to subjective bias. We present a fast, fully automated method for WMC segmentation using a cascade of reduced support vector machines (SVMs) with active learning. Data of 102 subjects was used in this study. Two MRI sequences (T1-weighted and FLAIR) and masks of manually outlined WMC from each subject were used for the image analysis. The segmentation framework comprises pre-processing, classification (training and core segmentation) and post-processing. After pre-processing, the model was trained on two subjects and tested on the remaining 100 subjects. The effectiveness and robustness of the classification was assessed using the receiver operating curve technique. The cascade of SVMs segmentation framework outputted accurate results with high sensitivity (90%) and specificity (99.5%) values, with the manually outlined WMC as reference. An algorithm for the segmentation of WMC is proposed. This is a completely competitive and fast automatic segmentation framework, capable of using different input sequences, without changes or restrictions of the image analysis algorithm.
  •  
20.
  •  
21.
  • Duits, Flora H., et al. (author)
  • The cerebrospinal fluid "Alzheimer profile": Easily said, but what does it mean?
  • 2014
  • In: Alzheimer's & Dementia. - : Elsevier. - 1552-5260 .- 1552-5279. ; 10:6, s. 713-723
  • Journal article (peer-reviewed)abstract
    • Background: We aimed to identify the most useful definition of the "cerebrospinal fluid Alzheimer profile," based on amyloid-beta(1-42) (A beta(42)), total tau, and phosphorylated tau (p-tau), for diagnosis and prognosis of Alzheimers disease (AD). Methods: We constructed eight Alzheimer profiles with previously published combinations, including regression formulas and simple ratios. We compared their diagnostic accuracy and ability to predict dementia due to AD in 1385 patients from the Amsterdam Dementia Cohort. Results were validated in an independent cohort (n = 1442). Results: Combinations outperformed individual biomarkers. Based on the sensitivity of the best performing regression formulas, cutoffs were chosen at 0.52 for the tau/A beta(42) ratio and 0.08 for the p-tau/A beta(42) ratio. Ratios performed similar to formulas (sensitivity, 91%-93%; specificity, 81%-84%). The same combinations best predicted cognitive decline in mild cognitive impairment patients. Validation confirmed these results, especially regarding the tau/A beta(42) ratio. Conclusions: A tau/A beta(42) ratio of greater than0.52 constitutes a robust cerebrospinal fluid Alzheimer profile. We recommend using this ratio to combine biomarkers.
  •  
22.
  • Eliassen, Ingvild Vøllo, et al. (author)
  • Regression-Based Cognitive Change Norms Applied in Biochemically Defined Predementia Alzheimer’s Disease
  • 2023
  • In: Neuropsychology. - : American Psychological Association (APA). - 0894-4105 .- 1931-1559. ; 37:1
  • Journal article (peer-reviewed)abstract
    • Objective: We aim to develop 2-year cognitive change norms for adults ages 41–84 for six cognitive tests, and to evaluate these norms in groups with AD biomarkers. Background: Practice effects are common in repeated neuropsychological testing. Not accounting for practice effects may obscure cognitive decline in early Alzheimer’s disease (AD). Method: We developed standardized regression-based change norms from normative samples consisting of healthy controls from the Dementia Disease Initiation study (n = 125), the Trønderbrain study (n = 57), and the Gothenburg mild cognitive impairment (MCI) study (n = 65). Norms were applied in a sample with cognitive symptoms (subjective cognitive decline or MCI) and AD cerebrospinal fluid (CSF) biomarkers (n = 246), classified according to the A/T/N system. Results: The change norms adjusted for pertinent demographics and practice effects. The group with cognitive complaints displayed a trend toward cognitive decline compared to the normative group, with the A+T/N+ subgroup showing the most marked decline. This was observed in tests of episodic memory and cognitive flexibility/divided attention. Conclusions: We present 2-year cognitive change norms for adults between 41 and 84 years, adjusted for practice and demographics. A web-based change norm calculator is provided.
  •  
23.
  • Enache, Daniela, et al. (author)
  • CAIDE Dementia Risk Score and biomarkers of neurodegeneration in memory clinic patients without dementia
  • 2016
  • In: Neurobiology of Aging. - : Elsevier BV. - 0197-4580 .- 1558-1497. ; 42, s. 124-131
  • Journal article (peer-reviewed)abstract
    • The aim of this study was to explore cross-sectional associations between Cardiovascular Risk Factors, Aging and Dementia Study (CAIDE) Dementia Risk Score and dementia-related cerebrospinal fluid and neuroimaging biomarkers in 724 patients without dementia from the Memory Clinic at Karolinska University Hospital, Huddinge, Sweden. We additionally evaluated the score's capacity to predict dementia. Two risk score versions were calculated: one including age, gender, obesity, hyperlipidemia, and hypertension; and one additionally including apolipoprotein E (APOE) ε4 carrier status. Cerebrospinal fluid was analyzed for amyloid β (Aβ), total tau, and phosphorylated tau. Visual assessments of medial temporal lobe atrophy (MTA), global cortical atrophy-frontal subscale, and Fazekas scale for white matter changes (WMC) were performed. Higher CAIDE Dementia Risk Score (version without APOE) was significantly associated with higher total tau, more severe MTA, WMC, and global cortical atrophy-frontal subscale. Higher CAIDE Dementia Risk Score (version with APOE) was associated with reduced Aβ, more severe MTA, and WMC. CAIDE Dementia Risk Score version with APOE seemed to predict dementia better in this memory clinic population with short follow-up than the version without APOE.
  •  
24.
  • Etminani, Kobra, 1984-, et al. (author)
  • A 3D deep learning model to predict the diagnosis of dementia with Lewy bodies, Alzheimers disease, and mild cognitive impairment using brain 18F-FDG PET
  • 2022
  • In: European Journal of Nuclear Medicine and Molecular Imaging. - New York : Springer. - 1619-7070 .- 1619-7089. ; 49, s. 563-584
  • Journal article (peer-reviewed)abstract
    • Purpose The purpose of this study is to develop and validate a 3D deep learning model that predicts the final clinical diagnosis of Alzheimers disease (AD), dementia with Lewy bodies (DLB), mild cognitive impairment due to Alzheimers disease (MCI-AD), and cognitively normal (CN) using fluorine 18 fluorodeoxyglucose PET (18F-FDG PET) and compare models performance to that of multiple expert nuclear medicine physicians readers. Materials and methods Retrospective 18F-FDG PET scans for AD, MCI-AD, and CN were collected from Alzheimers disease neuroimaging initiative (556 patients from 2005 to 2020), and CN and DLB cases were from European DLB Consortium (201 patients from 2005 to 2018). The introduced 3D convolutional neural network was trained using 90% of the data and externally tested using 10% as well as comparison to human readers on the same independent test set. The models performance was analyzed with sensitivity, specificity, precision, F1 score, receiver operating characteristic (ROC). The regional metabolic changes driving classification were visualized using uniform manifold approximation and projection (UMAP) and network attention. Results The proposed model achieved area under the ROC curve of 96.2% (95% confidence interval: 90.6-100) on predicting the final diagnosis of DLB in the independent test set, 96.4% (92.7-100) in AD, 71.4% (51.6-91.2) in MCI-AD, and 94.7% (90-99.5) in CN, which in ROC space outperformed human readers performance. The network attention depicted the posterior cingulate cortex is important for each neurodegenerative disease, and the UMAP visualization of the extracted features by the proposed model demonstrates the reality of development of the given disorders. Conclusion Using only 18F-FDG PET of the brain, a 3D deep learning model could predict the final diagnosis of the most common neurodegenerative disorders which achieved a competitive performance compared to the human readers as well as their consensus.
  •  
25.
  • Ferreira, Daniel, et al. (author)
  • β-Amyloid and tau biomarkers and clinical phenotype in dementia with Lewy bodies
  • 2020
  • In: Neurology. - 1526-632X. ; 95:24, s. 3257-3268
  • Journal article (peer-reviewed)abstract
    • OBJECTIVE: In a multicenter cohort of probable dementia with Lewy bodies (DLB), we tested the hypothesis that β-amyloid and tau biomarker positivity increases with age, which is modified by APOE genotype and sex, and that there are isolated and synergistic associations with the clinical phenotype. METHODS: We included 417 patients with DLB (age 45-93 years, 31% women). Positivity on β-amyloid (A+) and tau (T+) biomarkers was determined by CSF β-amyloid1-42 and phosphorylated tau in the European cohort and by Pittsburgh compound B and AV-1451 PET in the Mayo Clinic cohort. Patients were stratified into 4 groups: A-T-, A+T-, A-T+, and A+T+. RESULTS: A-T- was the largest group (39%), followed by A+T- (32%), A+T+ (15%), and A-T+ (13%). The percentage of A-T- decreased with age, and A+ and T+ increased with age in both women and men. A+ increased more in APOE ε4 carriers with age than in noncarriers. A+ was the main predictor of lower cognitive performance when considered together with T+. T+ was associated with a lower frequency of parkinsonism and probable REM sleep behavior disorder. There were no significant interactions between A+ and T+ in relation to the clinical phenotype. CONCLUSIONS: Alzheimer disease pathologic changes are common in DLB and are associated with the clinical phenotype. β-Amyloid is associated with cognitive impairment, and tau pathology is associated with lower frequency of clinical features of DLB. These findings have important implications for diagnosis, prognosis, and disease monitoring, as well as for clinical trials targeting disease-specific proteins in DLB. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that in patients with probable DLB, β-amyloid is associated with lower cognitive performance and tau pathology is associated with lower frequency of clinical features of DLB.
  •  
26.
  • Festari, Cristina, et al. (author)
  • European consensus for the diagnosis of MCI and mild dementia : Preparatory phase
  • 2023
  • In: Alzheimer's and Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 19:5, s. 1729-1741
  • Journal article (peer-reviewed)abstract
    • Introduction: Etiological diagnosis of neurocognitive disorders of middle-old age relies on biomarkers, although evidence for their rational use is incomplete. A European task force is defining a diagnostic workflow where expert experience fills evidence gaps for biomarker validity and prioritization. We report methodology and preliminary results. Methods: Using a Delphi consensus method supported by a systematic literature review, 22 delegates from 11 relevant scientific societies defined workflow assumptions. Results: We extracted diagnostic accuracy figures from literature on the use of biomarkers in the diagnosis of main forms of neurocognitive disorders. Supported by this evidence, panelists defined clinical setting (specialist outpatient service), application stage (MCI-mild dementia), and detailed pre-assessment screening (clinical-neuropsychological evaluations, brain imaging, and blood tests). Discussion: The Delphi consensus on these assumptions set the stage for the development of the first pan-European workflow for biomarkers’ use in the etiological diagnosis of middle-old age neurocognitive disorders at MCI-mild dementia stages. Highlights: Rational use of biomarkers in neurocognitive disorders lacks consensus in Europe. A consensus of experts will define a workflow for the rational use of biomarkers. The diagnostic workflow will be patient-centered and based on clinical presentation. The workflow will be updated as new evidence accrues.
  •  
27.
  • Freund-Levi, Yvonne, 1956-, et al. (author)
  • Galantamine versus risperidone for agitation in people with dementia : a randomized, twelve-week, single-center study
  • 2014
  • In: Dementia and Geriatric Cognitive Disorders. - : S. Karger. - 1420-8008 .- 1421-9824. ; 38:3-4, s. 234-244
  • Journal article (peer-reviewed)abstract
    • AIMS: To examine the effects of galantamine and risperidone on agitation in patients with dementia.METHODS: A total of 100 patients with dementia and neuropsychiatric symptoms (mean age ± SD: 78.6 ± 7.5 years; 67% female) were included in this 12-week, randomized, parallel-group, controlled, single-center trial. The participants received galantamine (n = 50; target dose: 24 mg) or risperidone (n = 50; target dose: 1.5 mg) for 12 weeks.RESULTS: Both galantamine and risperidone treatment resulted in reduced agitation. However, risperidone showed a significant advantage over galantamine both at week 3 (mean difference in total Cohen-Mansfield Agitation Inventory score: 3.7 points; p = 0.03) and at week 12 (4.3 points; p = 0.01).CONCLUSIONS: Agitation improved in both groups, even if the treatment effects were more pronounced in the risperidone group; however, the effects on cognition and other aspects of tolerability were stronger with galantamine.
  •  
28.
  • Frisoni, Giovanni B., et al. (author)
  • European intersocietal recommendations for the biomarker-based diagnosis of neurocognitive disorders
  • 2024
  • In: The Lancet Neurology. - 1474-4422 .- 1474-4465. ; 23:3, s. 302-312
  • Research review (peer-reviewed)abstract
    • The recent commercialisation of the first disease-modifying drugs for Alzheimer's disease emphasises the need for consensus recommendations on the rational use of biomarkers to diagnose people with suspected neurocognitive disorders in memory clinics. Most available recommendations and guidelines are either disease-centred or biomarker-centred. A European multidisciplinary taskforce consisting of 22 experts from 11 European scientific societies set out to define the first patient-centred diagnostic workflow that aims to prioritise testing for available biomarkers in individuals attending memory clinics. After an extensive literature review, we used a Delphi consensus procedure to identify 11 clinical syndromes, based on clinical history and examination, neuropsychology, blood tests, structural imaging, and, in some cases, EEG. We recommend first-line and, if needed, second-line testing for biomarkers according to the patient's clinical profile and the results of previous biomarker findings. This diagnostic workflow will promote consistency in the diagnosis of neurocognitive disorders across European countries.
  •  
29.
  • Gibson, Lucy L, et al. (author)
  • NMDA Receptor Antibodies and Neuropsychiatric Symptoms in Parkinson's Disease.
  • 2023
  • In: The Journal of neuropsychiatry and clinical neurosciences. - : American Psychiatric Association Publishing. - 1545-7222 .- 0895-0172. ; 35:3, s. 236-243
  • Journal article (peer-reviewed)abstract
    • N-methyl-d-aspartate receptor (NMDAR) encephalitis is an autoantibody-mediated neurological syndrome with prominent cognitive and neuropsychiatric symptoms. The clinical relevance of NMDAR antibodies outside the context of encephalitis was assessed in this study.Plasma from patients with Parkinson's disease (PD) (N=108) and healthy control subjects (N=89) was screened at baseline for immunoglobulin A (IgA), IgM, and IgG NMDAR antibodies, phosphorylated tau 181 (p-tau181), and the neuroaxonal injury marker neurofilament light (NfL). Clinical assessment of the patients included measures of cognition (Mini-Mental State Examination [MMSE]) and neuropsychiatric symptoms (Hospital Anxiety and Depression Scale; Non-Motor Symptoms Scale for Parkinson's Disease). A subgroup of patients (N=61) was followed annually for up to 6 years.Ten (9%) patients with PD tested positive for NMDAR antibodies (IgA, N=5; IgM, N=6; IgG, N=0), and three (3%) healthy control subjects had IgM NMDAR antibodies; IgA NMDAR antibodies were detected significantly more commonly among patients with PD than healthy control subjects (χ2=4.23, df=1, p=0.04). Age, gender, and disease duration were not associated with NMDAR antibody positivity. Longitudinally, antibody-positive patients had significantly greater decline in annual MMSE scores when the analyses were adjusted for education, age, disease duration, p-tau181, NfL, and follow-up duration (adjusted R2=0.26, p=0.01). Neuropsychiatric symptoms were not associated with antibody status, and no associations were seen between NMDAR antibodies and p-tau181 or NfL levels.NMDAR antibodies were associated with greater cognitive impairment over time in patients with PD, independent of other pathological biomarkers, suggesting a potential contribution of these antibodies to cognitive decline in PD.
  •  
30.
  • Gonzalez, Maria C, et al. (author)
  • Association of Plasma p-tau181 and p-tau231 Concentrations With Cognitive Decline in Patients With Probable Dementia With Lewy Bodies.
  • 2022
  • In: JAMA neurology. - : American Medical Association (AMA). - 2168-6157 .- 2168-6149. ; 79:1, s. 32-37
  • Journal article (peer-reviewed)abstract
    • Plasma phosphorylated tau (p-tau) has proven to be an accurate biomarker for Alzheimer disease (AD) pathologic characteristics, offering a less expensive and less invasive alternative to cerebrospinal fluid (CSF) and positron emission tomography biomarkers for amyloid-β and tau. Alzheimer disease comorbid pathologic characteristics are common and are associated with more rapid cognitive decline in patients with dementia with Lewy bodies (DLB); therefore, it is anticipated that plasma p-tau concentrations may have utility in assessing cognitive impairment in individuals with this disorder.To measure the concentrations of plasma p-tau (p-tau181 and p-tau231) and evaluate their associations with cognitive decline in individuals with probable DLB.This multicenter longitudinal cohort study included participants from the European-DLB (E-DLB) Consortium cohort enrolled at 10 centers with harmonized diagnostic procedures from January 1, 2002, to December 31, 2020, with up to 5 years of follow-up. A total of 1122 participants with plasma samples were available. Participants with acute delirium or terminal illness and patients with other previous major psychiatric or neurologic disorders were excluded, leaving a cohort of 987 clinically diagnosed participants with probable DLB (n=371), Parkinson disease (n=204), AD (n=207), as well as healthy controls (HCs) (n=205).The main outcome was plasma p-tau181 and p-tau231 levels measured with in-house single molecule array assays. The Mini-Mental State Examination (MMSE) was used to measure cognition.Among this cohort of 987 patients (512 men [51.9%]; mean [SD] age, 70.0 [8.8] years), patients with DLB did not differ significantly regarding age, sex, or years of education from those in the AD group, but the DLB group was older than the HC group and included more men than the AD and HC groups. Baseline concentrations of plasma p-tau181 and p-tau231 in patients with DLB were significantly higher than those in the HC group but lower than in the AD group and similar to the Parkinson disease group. Higher plasma concentrations of both p-tau markers were found in a subgroup of patients with DLB with abnormal CSF amyloid-β42 levels compared with those with normal levels (difference in the groups in p-tau181, -3.61 pg/mL; 95% CI, -5.43 to -1.79 pg/mL; P=.049; difference in the groups in p-tau231, -2.51 pg/mL; 95% CI, -3.63 to -1.39 pg/mL; P=.02). There was no difference between p-tau181 level and p-tau231 level across confirmed AD pathologic characteristcs based on reduced Aβ42 level in CSF in individuals with DLB. In DLB, a significant association was found between higher plasma p-tau181 and p-tau231 levels and lower MMSE scores at baseline (for p-tau181, -0.092 MMSE points; 95% CI, -0.12 to -0.06 MMSE points; P=.001; for p-tau231, -0.16 MMSE points; 95% CI, -0.21 to -0.12 MMSE points; P<.001), as well as more rapid MMSE decline over time. Plasma p-tau181 level was associated with a decrease of -0.094 MMSE points per year (95% CI, -0.144 to -0.052 MMSE points; P=.02), whereas plasma p-tau231 level was associated with an annual decrease of -0.130 MMSE points (95% CI, -0.201 to -0.071 MMSE points; P=.02), after adjusting for sex and age.This study suggests that plasma p-tau181 and p-tau231 levels may be used as cost-effective and accessible biomarkers to assess cognitive decline in individuals with DLB.
  •  
31.
  • Gonzalez, Maria Camila, et al. (author)
  • Cognitive and motor decline in dementia with lewy bodies and Parkinson's disease dementia
  • 2023
  • In: Movement Disorders Clinical Practice. - : John Wiley & Sons. - 2330-1619. ; 10:6, s. 980-986
  • Journal article (peer-reviewed)abstract
    • Background: There is a need to better understand the rate of cognitive and motor decline of Dementia with Lewy bodies (DLB) and Parkinson's disease Dementia (PDD).Objectives: To compare the rate of cognitive and motor decline in patients with DLB and PDD from the E-DLB Consortium and the Parkinson's Incidence Cohorts Collaboration (PICC) Cohorts.Methods: The annual change in MMSE and MDS-UPDRS part III was estimated using linear mixed regression models in patients with at least one follow-up (DLB n = 837 and PDD n = 157).Results: When adjusting for confounders, we found no difference in the annual change in MMSE between DLB and PDD (−1.8 [95% CI −2.3, −1.3] vs. −1.9 [95% CI −2.6, −1.2] [P = 0.74]). MDS-UPDRS part III showed nearly identical annual changes (DLB 4.8 [95% CI 2.1, 7.5]) (PDD 4.8 [95% CI 2.7, 6.9], [P = 0.98]).Conclusions: DLB and PDD showed similar rates of cognitive and motor decline. This is relevant for future clinical trial designs.
  •  
32.
  • Gonzalez-Ortiz, Fernando, 1990, et al. (author)
  • Plasma brain-derived tau is an amyloid-associated neurodegeneration biomarker in Alzheimer's disease.
  • 2024
  • In: Nature communications. - 2041-1723. ; 15:1
  • Journal article (peer-reviewed)abstract
    • Staging amyloid-beta (Aβ) pathophysiology according to the intensity of neurodegeneration could identify individuals at risk for cognitive decline in Alzheimer's disease (AD). In blood, phosphorylated tau (p-tau) associates with Aβ pathophysiology but an AD-type neurodegeneration biomarker has been lacking. In this multicenter study (n=1076), we show that brain-derived tau (BD-tau) in blood increases according to concomitant Aβ ("A") and neurodegeneration ("N") abnormalities (determined using cerebrospinal fluid biomarkers); We used blood-based A/N biomarkers to profile the participants in this study; individuals with blood-based p-tau+/BD-tau+ profiles had the fastest cognitive decline and atrophy rates, irrespective of the baseline cognitive status. Furthermore, BD-tau showed no or much weaker correlations with age, renal function, other comorbidities/risk factors and self-identified race/ethnicity, compared with other blood biomarkers. Here we show that blood-based BD-tau is a biomarker for identifying Aβ-positive individuals at risk of short-term cognitive decline and atrophy, with implications for clinical trials and implementation of anti-Aβ therapies.
  •  
33.
  • Gurholt, Tiril P., et al. (author)
  • Linking sarcopenia, brain structure and cognitive performance: a large-scale UK Biobank study
  • 2024
  • In: Brain Communications. - : OXFORD UNIV PRESS. - 2632-1297. ; 6:2
  • Journal article (peer-reviewed)abstract
    • Sarcopenia refers to age-related loss of muscle mass and function and is related to impaired somatic and brain health, including cognitive decline and Alzheimer's disease. However, the relationships between sarcopenia, brain structure and cognition are poorly understood. Here, we investigate the associations between sarcopenic traits, brain structure and cognitive performance. We included 33 709 UK Biobank participants (54.2% female; age range 44-82 years) with structural and diffusion magnetic resonance imaging, thigh muscle fat infiltration (n = 30 561) from whole-body magnetic resonance imaging (muscle quality indicator) and general cognitive performance as indicated by the first principal component of a principal component analysis across multiple cognitive tests (n = 22 530). Of these, 1703 participants qualified for probable sarcopenia based on low handgrip strength, and we assigned the remaining 32 006 participants to the non-sarcopenia group. We used multiple linear regression to test how sarcopenic traits (probable sarcopenia versus non-sarcopenia and percentage of thigh muscle fat infiltration) relate to cognitive performance and brain structure (cortical thickness and area, white matter fractional anisotropy and deep and lower brain volumes). Next, we used structural equation modelling to test whether brain structure mediated the association between sarcopenic and cognitive traits. We adjusted all statistical analyses for confounders. We show that sarcopenic traits (probable sarcopenia versus non-sarcopenia and muscle fat infiltration) are significantly associated with lower cognitive performance and various brain magnetic resonance imaging measures. In probable sarcopenia, for the included brain regions, we observed widespread significant lower white matter fractional anisotropy (77.1% of tracts), predominantly lower regional brain volumes (61.3% of volumes) and thinner cortical thickness (37.9% of parcellations), with |r| effect sizes in (0.02, 0.06) and P-values in (0.0002, 4.2e(-29)). In contrast, we observed significant associations between higher muscle fat infiltration and widespread thinner cortical thickness (76.5% of parcellations), lower white matter fractional anisotropy (62.5% of tracts) and predominantly lower brain volumes (35.5% of volumes), with |r| effect sizes in (0.02, 0.07) and P-values in (0.0002, 1.9e(-31)). The regions showing the most significant effect sizes across the cortex, white matter and volumes were of the sensorimotor system. Structural equation modelling analysis revealed that sensorimotor brain regions mediate the link between sarcopenic and cognitive traits [probable sarcopenia: P-values in (0.0001, 1.0e-11); muscle fat infiltration: P-values in (7.7e(-05), 1.7e(-12))]. Our findings show significant associations between sarcopenic traits, brain structure and cognitive performance in a middle-aged and older adult population. Mediation analyses suggest that regional brain structure mediates the association between sarcopenic and cognitive traits, with potential implications for dementia development and prevention.
  •  
34.
  • Holmgren, Simon, et al. (author)
  • Neuropsychiatric symptoms in dementia : a role for neuroinflammation?
  • 2014
  • In: Brain Research Bulletin. - : Elsevier. - 0361-9230 .- 1873-2747. ; 108, s. 88-93
  • Journal article (peer-reviewed)abstract
    • Dementia is characterized by a progressive cognitive decline and neuropsychiatric symptoms (NPSD) such as agitation, apathy and sleeping problems. There is some evidence of activation of inflammatory pathways in the brain in dementia, but little research has been performed regarding the role of neuroinflammation in NPSD, which might represent a potential novel target for treatment. The aim of this study was to examine the possible association between NPSD and cerebrospinal fluid (CSF) levels of the cytokines IL-6, TNF-α and IL-10, and the cytokine receptor sIL-1RII, in patients with dementia and NPSD. Ninety-four patients (mean age 79±8; 67% female) with a score on the neuropsychiatric inventory (NPI) ≥10 points, were included. Clinical assessment included administration of NPI, the mini-mental state examination (MMSE) and the Cohen-Mansfield agitation inventory (CMAI). The cytokine levels in CSF samples were analysed by enzyme-linked immunosorbent assay. Correlations were statistically examined using Spearman's rank correlation coefficient (r), and simple- and multiple-linear regression. The anti-inflammatory cytokine IL-10 showed reverse correlations with total NPI score (NPI-total=-0.001, t(90)= 8.50, p=0.004) and NPI sub-items agitation (agitation=-0.007, t(90)=7.02, p=0.009) and night-time behaviour (night time behaviour=-0.006, t(90)=6.34, p=0.01). There was a trend towards reverse correlation between IL-10 and depression (depression=-0.004, t(90)=2.96, p=0.09). Also, the soluble cytokine receptor sIL-1RII showed a trend towards correlation with apathy (apathy=0.82, t(82)=3.62, p=0.06). The levels of IL-6 showed no significant correlations with NPSD. Levels of TNF-α were non-detectable. In Alzheimer's disease (AD) subjects (n=33), IL-6 showed reverse correlation with anxiety (r=-0.35, p=0.049). In mixed AD subjects (n=26), IL-10 showed reverse correlations with the total NPI score (r=-0.46, p=0.02) and depression (r=-0.45, p=0.02). The findings indicate a relationship between neuroinflammation and neuropsychiatric symptoms in AD in which anti-inflammatory signalling by IL-10 is beneficial from a mental health perspective.
  •  
35.
  • Holmgren, Simon, et al. (author)
  • Neuropsychiatric Symptoms in Dementia : Considering a Clinical Role for Electroencephalography
  • 2022
  • In: The Journal of Neuropsychiatry and Clinical Neurosciences. - : American Psychiatric Association Publishing, Inc.. - 0895-0172 .- 1545-7222. ; 34:3, s. 214-223
  • Journal article (peer-reviewed)abstract
    • OBJECTIVE: Degenerative dementia is characterized by progressive cognitive decline and neuropsychiatric symptoms. People with Alzheimer's disease (AD), the most common cause of dementia, show synaptic loss and disruption of functional brain networks along with neuritic plaques and neurofibrillary tangles. Electroencephalography (EEG) directly reflects synaptic activity, and among patients with AD it is associated with slowing of background activity. The purpose of this study was to identify associations between neuropsychiatric symptoms and EEG in patients with dementia and to determine whether EEG parameters could be used for clinical assessment of pharmacological treatment of neuropsychiatric symptoms in dementia (NPSD) with galantamine or risperidone.METHODS: Seventy-two patients with EEG recordings and a score ≥10 on the Neuropsychiatric Inventory (NPI) were included. Clinical assessments included administration of the NPI, the Mini-Mental State Examination (MMSE), and the Cohen-Mansfield Agitation Inventory (CMAI). Patients underwent EEG examinations at baseline and after 12 weeks of treatment with galantamine or risperidone. EEG frequency analysis was performed. Correlations between EEG and assessment scale scores were statistically examined, as were EEG changes from baseline to the week 12 visit and the relationship with NPI, CMAI, and MMSE scores.RESULTS: Significant correlations were found between NPI agitation and delta EEG frequencies at baseline and week 12. No other consistent and significant relationships were observed between NPSD and EEG at baseline, after NPSD treatment, or in the change in EEG from baseline to follow-up.CONCLUSIONS: The limited informative findings in this study suggest that there exists a complex relationship between NPSD and EEG; hence, it is difficult to evaluate and use EEG for clinical assessment of pharmacological NPSD treatment.
  •  
36.
  • Huber, Maria, et al. (author)
  • Metabolic correlates of dopaminergic loss in dementia with lewy bodies
  • 2020
  • In: Movement Disorders. - : WILEY. - 0885-3185 .- 1531-8257. ; 35, s. 595-605
  • Journal article (peer-reviewed)abstract
    • Background Striatal dopamine deficiency and metabolic changes are well-known phenomena in dementia with Lewy bodies and can be quantified in vivo by I-123-Ioflupane brain single-photon emission computed tomography of dopamine transporter and F-18-fluorodesoxyglucose PET. However, the linkage between both biomarkers is ill-understood. Objective We used the hitherto largest study cohort of combined imaging from the European consortium to elucidate the role of both biomarkers in the pathophysiological course of dementia with Lewy bodies. Methods We compared striatal dopamine deficiency and glucose metabolism of 84 dementia with Lewy body patients and comparable healthy controls. After normalization of data, we tested their correlation by region-of-interest-based and voxel-based methods, controlled for study center, age, sex, education, and current cognitive impairment. Metabolic connectivity was analyzed by inter-region coefficients stratified by dopamine deficiency and compared to healthy controls. Results There was an inverse relationship between striatal dopamine availability and relative glucose hypermetabolism, pronounced in the basal ganglia and in limbic regions. With increasing dopamine deficiency, metabolic connectivity showed strong deteriorations in distinct brain regions implicated in disease symptoms, with greatest disruptions in the basal ganglia and limbic system, coincident with the pattern of relative hypermetabolism. Conclusions Relative glucose hypermetabolism and disturbed metabolic connectivity of limbic and basal ganglia circuits are metabolic correlates of dopamine deficiency in dementia with Lewy bodies. Identification of specific metabolic network alterations in patients with early dopamine deficiency may serve as an additional supporting biomarker for timely diagnosis of dementia with Lewy bodies. (c) 2019 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.
  •  
37.
  • Jansen, Willemijn J, et al. (author)
  • Association of Cerebral Amyloid-β Aggregation With Cognitive Functioning in Persons Without Dementia.
  • 2018
  • In: JAMA psychiatry. - : American Medical Association (AMA). - 2168-6238 .- 2168-622X. ; 75:1, s. 84-95
  • Journal article (peer-reviewed)abstract
    • Cerebral amyloid-β aggregation is an early event in Alzheimer disease (AD). Understanding the association between amyloid aggregation and cognitive manifestation in persons without dementia is important for a better understanding of the course of AD and for the design of prevention trials.To investigate whether amyloid-β aggregation is associated with cognitive functioning in persons without dementia.This cross-sectional study included 2908 participants with normal cognition and 4133 with mild cognitive impairment (MCI) from 53 studies in the multicenter Amyloid Biomarker Study. Normal cognition was defined as having no cognitive concerns for which medical help was sought and scores within the normal range on cognitive tests. Mild cognitive impairment was diagnosed according to published criteria. Study inclusion began in 2013 and is ongoing. Data analysis was performed in January 2017.Global cognitive performance as assessed by the Mini-Mental State Examination (MMSE) and episodic memory performance as assessed by a verbal word learning test. Amyloid aggregation was measured with positron emission tomography or cerebrospinal fluid biomarkers and dichotomized as negative (normal) or positive (abnormal) according to study-specific cutoffs. Generalized estimating equations were used to examine the association between amyloid aggregation and low cognitive scores (MMSE score ≤27 or memory z score≤-1.28) and to assess whether this association was moderated by age, sex, educational level, or apolipoprotein E genotype.Among 2908 persons with normal cognition (mean [SD] age, 67.4 [12.8] years), amyloid positivity was associated with low memory scores after age 70 years (mean difference in amyloid positive vs negative, 4% [95% CI, 0%-7%] at 72 years and 21% [95% CI, 10%-33%] at 90 years) but was not associated with low MMSE scores (mean difference, 3% [95% CI, -1% to 6%], P=.16). Among 4133 patients with MCI (mean [SD] age, 70.2 [8.5] years), amyloid positivity was associated with low memory (mean difference, 16% [95% CI, 12%-20%], P<.001) and low MMSE (mean difference, 14% [95% CI, 12%-17%], P<.001) scores, and this association decreased with age. Low cognitive scores had limited utility for screening of amyloid positivity in persons with normal cognition and those with MCI. In persons with normal cognition, the age-related increase in low memory score paralleled the age-related increase in amyloid positivity with an intervening period of 10 to 15 years.Although low memory scores are an early marker of amyloid positivity, their value as a screening measure for early AD among persons without dementia is limited.
  •  
38.
  • Jansen, Willemijn J, et al. (author)
  • Prevalence Estimates of Amyloid Abnormality Across the Alzheimer Disease Clinical Spectrum.
  • 2022
  • In: JAMA neurology. - : American Medical Association (AMA). - 2168-6157 .- 2168-6149. ; 79:3, s. 228-243
  • Journal article (peer-reviewed)abstract
    • One characteristic histopathological event in Alzheimer disease (AD) is cerebral amyloid aggregation, which can be detected by biomarkers in cerebrospinal fluid (CSF) and on positron emission tomography (PET) scans. Prevalence estimates of amyloid pathology are important for health care planning and clinical trial design.To estimate the prevalence of amyloid abnormality in persons with normal cognition, subjective cognitive decline, mild cognitive impairment, or clinical AD dementia and to examine the potential implications of cutoff methods, biomarker modality (CSF or PET), age, sex, APOE genotype, educational level, geographical region, and dementia severity for these estimates.This cross-sectional, individual-participant pooled study included participants from 85 Amyloid Biomarker Study cohorts. Data collection was performed from January 1, 2013, to December 31, 2020. Participants had normal cognition, subjective cognitive decline, mild cognitive impairment, or clinical AD dementia. Normal cognition and subjective cognitive decline were defined by normal scores on cognitive tests, with the presence of cognitive complaints defining subjective cognitive decline. Mild cognitive impairment and clinical AD dementia were diagnosed according to published criteria.Alzheimer disease biomarkers detected on PET or in CSF.Amyloid measurements were dichotomized as normal or abnormal using cohort-provided cutoffs for CSF or PET or by visual reading for PET. Adjusted data-driven cutoffs for abnormal amyloid were calculated using gaussian mixture modeling. Prevalence of amyloid abnormality was estimated according to age, sex, cognitive status, biomarker modality, APOE carrier status, educational level, geographical location, and dementia severity using generalized estimating equations.Among the 19097 participants (mean [SD] age, 69.1 [9.8] years; 10148 women [53.1%]) included, 10139 (53.1%) underwent an amyloid PET scan and 8958 (46.9%) had an amyloid CSF measurement. Using cohort-provided cutoffs, amyloid abnormality prevalences were similar to 2015 estimates for individuals without dementia and were similar across PET- and CSF-based estimates (24%; 95% CI, 21%-28%) in participants with normal cognition, 27% (95% CI, 21%-33%) in participants with subjective cognitive decline, and 51% (95% CI, 46%-56%) in participants with mild cognitive impairment, whereas for clinical AD dementia the estimates were higher for PET than CSF (87% vs 79%; mean difference, 8%; 95% CI, 0%-16%; P=.04). Gaussian mixture modeling-based cutoffs for amyloid measures on PET scans were similar to cohort-provided cutoffs and were not adjusted. Adjusted CSF cutoffs resulted in a 10% higher amyloid abnormality prevalence than PET-based estimates in persons with normal cognition (mean difference, 9%; 95% CI, 3%-15%; P=.004), subjective cognitive decline (9%; 95% CI, 3%-15%; P=.005), and mild cognitive impairment (10%; 95% CI, 3%-17%; P=.004), whereas the estimates were comparable in persons with clinical AD dementia (mean difference, 4%; 95% CI, -2% to 9%; P=.18).This study found that CSF-based estimates using adjusted data-driven cutoffs were up to 10% higher than PET-based estimates in people without dementia, whereas the results were similar among people with dementia. This finding suggests that preclinical and prodromal AD may be more prevalent than previously estimated, which has important implications for clinical trial recruitment strategies and health care planning policies.
  •  
39.
  • Jansen, Willemijn J, et al. (author)
  • Prevalence of cerebral amyloid pathology in persons without dementia: a meta-analysis.
  • 2015
  • In: JAMA. - : American Medical Association (AMA). - 1538-3598 .- 0098-7484. ; 313:19, s. 1924-38
  • Journal article (peer-reviewed)abstract
    • Cerebral amyloid-β aggregation is an early pathological event in Alzheimer disease (AD), starting decades before dementia onset. Estimates of the prevalence of amyloid pathology in persons without dementia are needed to understand the development of AD and to design prevention studies.
  •  
40.
  • Jones, Emma L., et al. (author)
  • A Pilot Study Examining Associations between DYRK1A and alpha-Synuclein Dementias
  • 2012
  • In: Neurodegenerative Diseases. - : S. Karger AG. - 1660-2862 .- 1660-2854. ; 10:1-4, s. 229-231
  • Journal article (peer-reviewed)abstract
    • Background: DYRK1A is a kinase targeting several proteins associated with the pathology of dementias, including alpha-synuclein and amyloid precursor protein. It is not clear if DYRK1A genetics are associated with neurodegenerative conditions. Objective: To determine if DYRK1A also has a genetic association with alpha-synuclein dementias such as dementia with Lewy bodies and Parkinson's disease dementia. Methods: DNA samples from prospectively followed cohorts of control and dementia individuals were genotyped for the DYRK1A rs8126696 polymorphism. Results: The rs8126696 polymorphism altered the risk of developing an alpha-synuclein-associated dementia. Conclusion: DYRK1A could prove to be an important therapeutic target as it interacts with several proteins associated with the development of pathology in dementia. Copyright (C) 2012 S. Karger AG, Basel
  •  
41.
  • Kivipelto, Miia, et al. (author)
  • Nya kriterier för Alzheimers sjukdom: användning av biomarkörer ger tidigare och mer precis diagnos
  • 2011
  • In: Läkartidningen. - Stockholm : Läkartidningen förlag. - 0023-7205 .- 1652-7518. ; 108:32-33, s. 1491-1492
  • Journal article (peer-reviewed)abstract
    • Förslag till nya kriterier för olika stadier av Alzheimers sjukdom har (efter 27 år!) pub­licerats.De nya riktlinjerna inkluderar användning av nya biomarkörer och ger oss möjlighet att ställa diagnosen »preklinisk alzheimer« relativt långt in­nan de kliniska symtomen uppträder. Den nya diagnosen preklinisk alzheimer rekommenderas för närvarande endast för forskning.För närvarande saknas sjukdomsmodifierande behandling för alzheimer. Att ställa diagnosen preklinisk alzheimer på en frisk person, om än bara i forskning, blir därför en stor etisk fråga.En annan aspekt är hur hälso- och sjukvårdsapparaten klarar att utreda och ta hand om alla »nya« patienter.Vår slutsats är att kriterierna behöver valideras, men de kommer utan tvekan att leda till en tidigare och mer precis diagnos och dessutom vara till stor nytta när vi förhoppningsvis får nya sjukdomsmodifierande läkemedel.
  •  
42.
  • Kramberger, Milica Gregoric, et al. (author)
  • Cerebrospinal fluid alzheimer markers in depressed elderly dubjects with and without alzheimer's disease
  • 2012
  • In: Dementia and Geriatric Cognitive Disorders Extra. - : S. Karger AG. - 1664-5464. ; 2:1, s. 48-56
  • Journal article (peer-reviewed)abstract
    • Background: The aim of this study was to explore the relationship between cerebrospinal fluid Alzheimer's disease (AD) markers and depression in elderly people.Method: We included subjects with AD as well as persons with subjective cognitive impairment and normal cognition. Depression was assessed with the Cornell Scale for Depression in Dementia, and a cut-off score of >6 was used to define depression. Cerebrospinal fluid was analyzed using commercially available assays for β-amyloid 1-42, total tau, and phosphorylated tau 181.Result: A total of 183 participants (66.7% female) were included (92 with AD and 91 with subjective cognitive impairment), with a mean age (±SD) of 67.6 ± 7.4 years, a Mini-Mental State Examination score of 26.0 ± 4.0, and a median Cornell Scale for Depression in Dementia score of 5 (range 0-19). Depression scores were not associated with higher phosphorylated tau 181 and total tau or reduced β-amyloid 1-42 in AD or non-demented subjects.Conclusions: These results suggest that AD pathology does not contribute to depression, indicating that other factors may be more important. Further studies of the aetiology of depression in elderly people with and without AD are warranted.
  •  
43.
  • Kramberger, Milica G., et al. (author)
  • Long-Term Cognitive Decline in Dementia with Lewy Bodies in a Large Multicenter, International Cohort
  • 2017
  • In: Journal of Alzheimer's Disease. - 1387-2877 .- 1875-8908. ; 57:3, s. 787-795
  • Journal article (peer-reviewed)abstract
    • Background/Objective: The aim of this study was to describe the rate and clinical predictors of cognitive decline in dementia with Lewy bodies (DLB), and compare the findings with Alzheimer's disease (AD) and Parkinson's disease dementia (PDD) patients. Methods: Longitudinal scores for the Mini-Mental State Examination (MMSE) in 1,290 patients (835 DLB, 198 PDD, and 257 AD) were available from 18 centers with up to three years longitudinal data. Linear mixed effects analyses with appropriate covariates were used to model MMSE decline over time. Several subgroup analyses were performed, defined by anti-dementia medication use, baseline MMSE score, and DLB core features. Results: The mean annual decline in MMSE score was 2.1 points in DLB, compared to 1.6 in AD (p=0.07 compared to DLB) and 1.8 in PDD (p=0.19). Rates of decline were significantly higher in DLB compared to AD and PDD when baseline MMSE score was included as a covariate, and when only those DLB patients with an abnormal dopamine transporter SPECT scan were included. Decline was not predicted by sex, baseline MMSE score, or presence of specific DLB core features. Conclusions: The average annual decline in MMSE score in DLB is approximately two points. Although in the overall analyses there were no differences in the rate of decline between the three neurodegenerative disorders, there were indications of a more rapid decline in DLB than in AD and PDD. Further studies are needed to understand the predictors and mechanisms of cognitive decline in DLB.
  •  
44.
  • Lantero Rodriguez, Juan, et al. (author)
  • Plasma p-tau181 accurately predicts Alzheimer's disease pathology at least 8years prior to post-mortem and improves the clinical characterisation of cognitive decline.
  • 2020
  • In: Acta neuropathologica. - : Springer Science and Business Media LLC. - 1432-0533 .- 0001-6322. ; 140:3, s. 267-278
  • Journal article (peer-reviewed)abstract
    • The neuropathological confirmation of amyloid-β (Aβ) plaques and tau neurofibrillary tangles (NFT) remains the gold standard for a definitive diagnosis of Alzheimer's disease (AD). Nowadays, the in vivo diagnosis of AD is greatly aided by both cerebrospinal fluid (CSF) and positron emission tomography (PET) biomarkers. Although highly accurate, their broad implementation is restricted by high cost, limited accessibility and invasiveness. We recently developed a high-performance, ultrasensitive immunoassay for the quantification of tau phosphorylated at threonine-181 (p-tau181) in plasma, which identifies AD pathophysiology with high accuracy. However, it remains unclear whether plasma p-tau181, measured years before the death, can predict the eventual neuropathological confirmation of AD, and successfully discriminates AD from non-AD dementia pathologies. We studied a unique cohort of 115 individuals with longitudinal blood collections with clinical evaluation at 8, 4 and 2years prior to neuropathological assessment at death. The results demonstrate that plasma p-tau181 associates better with AD neuropathology and Braak staging than a clinical diagnosis 8years before post-mortem. Moreover, while all patients had a diagnosis of AD dementia during life, plasma p-tau181 proved to discriminate AD from non-AD pathologies with high accuracy (AUC=97.4%, 95% CI=94.1-100%) even 8years before death. Additionally, the longitudinal trajectory of plasma p-tau181 was assessed in all patients. We found that the main increases in plasma p-tau181 occurred between 8 and 4years prior to death in patients with AD neuropathology and later plateauing. In contrast, non-AD pathologies and controls exhibited minor, albeit significant, increases in p-tau181 up until death. Overall, our study demonstrates that plasma p-tau181 is highly predictive and specific of AD neuropathology years before post-mortem examination. These data add further support for the use of plasma p-tau181 to aid clinical management in primary care and recruitment for clinical trials.
  •  
45.
  • Larsson, Victoria, et al. (author)
  • Quality of Life and the Effect of Memantine in Dementia with Lewy Bodies and Parkinson's Disease Dementia.
  • 2011
  • In: Dementia and Geriatric Cognitive Disorders. - : S. Karger AG. - 1420-8008 .- 1421-9824. ; 32:4, s. 227-234
  • Journal article (peer-reviewed)abstract
    • Aim: To investigate quality of life (QOL) and the effect of memantine treatment in patients with Lewy body dementias. Methods: A secondary analysis of a randomized controlled study in 70 patients with Parkinson's disease dementia (PDD) or dementia with Lewy bodies (DLB) over 24 weeks using caregiver-rated QOL-Alzheimer's disease (AD) in domains according to the WHO's classification of health. Results: Baseline QOL shows lower ratings for body functions over environmental factors in DLB/PDD. Treatment with memantine significantly improves life as a whole compared to placebo and improves total QOL, body function and structure. Conclusion: This study shows that memantine improves QOL in Lewy body dementias. We also demonstrate important QOL patterns which can be used in clinical practice. Copyright (C) 2011 S. Karger AG, Basel
  •  
46.
  • Larsson, Victoria, et al. (author)
  • The effect of memantine on sleep behaviour in dementia with Lewy bodies and Parkinson's disease dementia.
  • 2010
  • In: International Journal of Geriatric Psychiatry. - : Wiley. - 1099-1166 .- 0885-6230. ; 25:10, s. 1030-1038
  • Journal article (peer-reviewed)abstract
    • OBJECTIVE: Two common and characteristic sleep disturbances have been described in dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD); excessive daytime sleepiness and REM sleep behaviour disorder (RBD). This study is an analysis of a secondary outcome measure of a larger study already reported, aimed to determine whether memantine has an effect on the sleep disturbances in DLB and PDD patients. METHODS: Patients with DLB or PDD were included in a placebo-controlled, randomised controlled study of memantine (20 mg per day) for 24 weeks. The Stavanger Sleep Questionnaire and the Epworth Sleepiness Scale were used to evaluate the effect on sleep disturbances. RESULTS: Forty two patients started treatment; 20 with memantine and 22 with placebo. The primary analysis was the comparison of change between the two groups during a 24-week period, using the modified ITT population (last observation carried forward). At 24 weeks, patients treated with memantine were less physically active during sleep while patients in the placebo group worsened. Mean difference between the groups (0.5 [0.05-0.90]) was significant (p = 0.006). No significant change was observed in severity of excessive daytime sleepiness. CONCLUSIONS: Memantine decreases probable REM sleep behaviour disorder in patients with DLB and PDD. Both diagnostic groups contributed equally to the outcome.
  •  
47.
  • Lleó, Alberto, et al. (author)
  • Cerebrospinal fluid biomarkers in trials for Alzheimer and Parkinson diseases.
  • 2015
  • In: Nature reviews. Neurology. - : Springer Science and Business Media LLC. - 1759-4766 .- 1759-4758. ; 11, s. 41-55
  • Research review (peer-reviewed)abstract
    • Alzheimer disease (AD) and Parkinson disease (PD) are the most common neurodegenerative disorders. For both diseases, early intervention is thought to be essential to the success of disease-modifying treatments. Cerebrospinal fluid (CSF) can reflect some of the pathophysiological changes that occur in the brain, and the number of CSF biomarkers under investigation in neurodegenerative conditions has grown rapidly in the past 20 years. In AD, CSF biomarkers are increasingly being used in clinical practice, and have been incorporated into the majority of clinical trials to demonstrate target engagement, to enrich or stratify patient groups, and to find evidence of disease modification. In PD, CSF biomarkers have not yet reached the clinic, but are being studied in patients with parkinsonism, and are being used in clinical trials either to monitor progression or to demonstrate target engagement and downstream effects of drugs. CSF biomarkers might also serve as surrogate markers of clinical benefit after a specific therapeutic intervention, although additional data are required. It is anticipated that CSF biomarkers will have an important role in trials aimed at disease modification in the near future. In this Review, we provide an overview of CSF biomarkers in AD and PD, and discuss their role in clinical trials.
  •  
48.
  • Lord, Jodie, et al. (author)
  • A genome-wide association study of plasma phosphorylated tau181
  • 2021
  • In: Neurobiology of aging. - : Elsevier BV. - 1558-1497 .- 0197-4580. ; 106
  • Journal article (peer-reviewed)abstract
    • Plasma phosphorylated tau at threonine-181 (P-tau181) demonstrates promise as an accessible blood-based biomarker specific to Alzheimer's Disease (AD), with levels recently demonstrating high predictive accuracy for AD-relevant pathology. The genetic underpinnings of P-tau181 levels, however, remain elusive. This study presents the first genome-wide association study of plasma P-tau181 in a total sample of 1153 participants from 2 independent cohorts. No loci, other than those within the APOE genomic region (lead variant=rs429358, beta=0.32, p =8.44×10-25) demonstrated association with P-tau181 at genome-wide significance (p < 5×10-08), though rs60872856 on chromosome 2 came close (beta=-0.28, p=3.23×10-07, nearest gene=CYTIP). As the APOE ε4 allele is already a well-established genetic variant associated with AD, this study found no evidence of novel genetic associations relevant to plasma P-tau181, though presents rs60872856 on chromosome 2 as a candidate locus to be further evaluated in future larger size GWAS.
  •  
49.
  • Martinez-Martin, Pablo, et al. (author)
  • Gender-related differences in the burden of non-motor symptoms in Parkinson's disease
  • 2012
  • In: Journal of Neurology. - : Springer Science and Business Media LLC. - 1432-1459 .- 0340-5354. ; 259:8, s. 1639-1647
  • Journal article (peer-reviewed)abstract
    • Differences in the expression of non-motor symptoms (NMS) by Parkinson's disease (PD) patients may have important implications for their management and prognosis. Gender is a basic epidemiological variable that could influence such expression. The present study evaluated the prevalence and severity of NMS by gender in an international sample of 951 PD patients, 62.63% males, using the non-motor symptoms scale (NMSS). Assessments for motor impairment and complications, global severity, and health state were also applied. All disease stages were included. No significant gender differences were found for demographic and clinical characteristics. For the entire sample, the most prevalent symptoms were Nocturia (64.88%) and Fatigue (62.78%) and the most prevalent affected domains were Sleep/Fatigue (84.02%) and Miscellaneous (82.44%). Fatigue, feelings of nervousness, feelings of sadness, constipation, restless legs, and pain were more common and severe in women. On the contrary, daytime sleepiness, dribbling saliva, interest in sex, and problems having sex were more prevalent and severe in men. Regarding the NMSS domains, Mood/Apathy and Miscellaneous problems (pain, loss of taste or smell, weight change, and excessive sweating) were predominantly affected in women and Sexual dysfunction in men. No other significant differences by gender were observed. To conclude, in this study significant differences between men and women in prevalence and severity of fatigue, mood, sexual and digestive problems, pain, restless legs, and daytime sleepiness were found. Gender-related patterns of NMS involvement may be relevant for clinical trials in PD.
  •  
50.
  • Mattsson, Niklas, 1979, et al. (author)
  • CSF biomarkers and incipient Alzheimer disease in patients with mild cognitive impairment.
  • 2009
  • In: JAMA : the journal of the American Medical Association. - : American Medical Association (AMA). - 1538-3598 .- 0098-7484. ; 302:4, s. 385-93
  • Journal article (peer-reviewed)abstract
    • CONTEXT: Small single-center studies have shown that cerebrospinal fluid (CSF) biomarkers may be useful to identify incipient Alzheimer disease (AD) in patients with mild cognitive impairment (MCI), but large-scale multicenter studies have not been conducted. OBJECTIVE: To determine the diagnostic accuracy of CSF beta-amyloid(1-42) (Abeta42), total tau protein (T-tau), and tau phosphorylated at position threonine 181 (P-tau) for predicting incipient AD in patients with MCI. DESIGN, SETTING, AND PARTICIPANTS: The study had 2 parts: a cross-sectional study involving patients with AD and controls to identify cut points, followed by a prospective cohort study involving patients with MCI, conducted 1990-2007. A total of 750 individuals with MCI, 529 with AD, and 304 controls were recruited by 12 centers in Europe and the United States. Individuals with MCI were followed up for at least 2 years or until symptoms had progressed to clinical dementia. MAIN OUTCOME MEASURES: Sensitivity, specificity, positive and negative likelihood ratios (LRs) of CSF Abeta42, T-tau, and P-tau for identifying incipient AD. RESULTS: During follow-up, 271 participants with MCI were diagnosed with AD and 59 with other dementias. The Abeta42 assay in particular had considerable intersite variability. Patients who developed AD had lower median Abeta42 (356; range, 96-1075 ng/L) and higher P-tau (81; range, 15-183 ng/L) and T-tau (582; range, 83-2174 ng/L) levels than MCI patients who did not develop AD during follow-up (579; range, 121-1420 ng/L for Abeta42; 53; range, 15-163 ng/L for P-tau; and 294; range, 31-2483 ng/L for T-tau, P < .001). The area under the receiver operating characteristic curve was 0.78 (95% confidence interval [CI], 0.75-0.82) for Abeta42, 0.76 (95% CI, 0.72-0.80) for P-tau, and 0.79 (95% CI, 0.76-0.83) for T-tau. Cut-offs with sensitivity set to 85% were defined in the AD and control groups and tested in the MCI group, where the combination of Abeta42/P-tau ratio and T-tau identified incipient AD with a sensitivity of 83% (95% CI, 78%-88%), specificity 72% (95% CI, 68%-76%), positive LR, 3.0 (95% CI, 2.5-3.4), and negative LR, 0.24 (95% CI, 0.21-0.28). The positive predictive value was 62% and the negative predictive value was 88%. CONCLUSIONS: This multicenter study found that CSF Abeta42, T-tau, and P-tau identify incipient AD with good accuracy, but less accurately than reported from single-center studies. Intersite assay variability highlights a need for standardization of analytical techniques and clinical procedures.
  •  
Skapa referenser, mejla, bekava och länka
  • Result 1-50 of 71
Type of publication
journal article (67)
research review (3)
conference paper (1)
Type of content
peer-reviewed (70)
other academic/artistic (1)
Author/Editor
Aarsland, Dag (71)
Blennow, Kaj, 1958 (22)
Zetterberg, Henrik, ... (22)
Londos, Elisabet (15)
Ballard, Clive (13)
Kramberger, Milica G ... (13)
show more...
Lemstra, Afina W. (12)
Vandenberghe, Rik (12)
Frisoni, Giovanni B. (12)
Hansson, Oskar (11)
Fladby, Tormod (11)
Pilotto, Andrea (10)
Winblad, Bengt (10)
Hye, Abdul (10)
Nobili, Flavio (10)
Minthon, Lennart (9)
Padovani, Alessandro (9)
Tsolaki, Magda (9)
Scheltens, Philip (9)
van der Flier, Wiesj ... (9)
Freund-Levi, Yvonne, ... (9)
Blanc, Frédéric (8)
Ashton, Nicholas J. (8)
Lleó, Alberto (8)
Visser, Pieter Jelle (8)
Garibotto, Valentina (8)
Abdelnour, Carla (7)
Marcusson, Jan (7)
Teunissen, Charlotte ... (7)
Karikari, Thomas (7)
Parnetti, Lucilla (7)
Bonanni, Laura (7)
Rabinovici, Gil D (7)
Hampel, Harald (7)
Westman, Eric (6)
Wallin, Anders, 1950 (6)
Van Laere, Koen (6)
Molinuevo, José Luis (6)
Alcolea, Daniel (6)
Mroczko, Barbara (6)
Waldemar, Gunhild (6)
Rowe, Christopher C (6)
Nicastro, Nicolas (6)
Bauckneht, Matteo (6)
Chincarini, Andrea (6)
Brendel, Matthias (6)
Rominger, Axel (6)
Bruffaerts, Rose (6)
Trost, Maja (6)
Camacho, Valle (6)
show less...
University
Karolinska Institutet (62)
University of Gothenburg (33)
Lund University (28)
Linköping University (11)
Örebro University (10)
Stockholm University (4)
show more...
Umeå University (3)
Jönköping University (3)
Halmstad University (2)
Royal Institute of Technology (1)
Uppsala University (1)
show less...
Language
English (70)
Swedish (1)
Research subject (UKÄ/SCB)
Medical and Health Sciences (70)
Natural sciences (1)
Engineering and Technology (1)
Social Sciences (1)

Year

Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.

 
pil uppåt Close

Copy and save the link in order to return to this view