| 31. |
- Handels, Ron L. H., et al.
(författare)
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Predicting progression to dementia in persons with mild cognitive impairment using cerebrospinal fluid markers
- 2017
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Ingår i: Alzheimer's & Dementia. - : Elsevier. - 1552-5260 .- 1552-5279. ; 13:8, s. 903-912
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: We aimed to determine the added value of cerebrospinal fluid (CSF) to clinical and imaging tests to predict progression from mild cognitive impairment (MCI) to any type of dementia.METHODS: The risk of progression to dementia was estimated using two logistic regression models based on 250 MCI participants: the first included standard clinical measures (demographic, clinical, and imaging test information) without CSF biomarkers, and the second included standard clinical measures with CSF biomarkers.RESULTS: Adding CSF improved predictive accuracy with 0.11 (scale from 0-1). Of all participants, 136 (54%) had a change in risk score of 0.10 or higher (which was considered clinically relevant), of whom in 101, it was in agreement with their dementia status at follow-up.DISCUSSION: An individual person's risk of progression from MCI to dementia can be improved by relying on CSF biomarkers in addition to recommended clinical and imaging tests for usual care.
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| 32. |
- Hjorth, Erik, et al.
(författare)
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Immunomodulation of microglia by docosahexaenoic acid and eicosapentaenoic acid.
- 2012
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Ingår i: Current opinion in clinical nutrition and metabolic care. - : Lippincott Williams & Wilkins. - 1363-1950 .- 1473-6519. ; 15:2, s. 134-143
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Forskningsöversikt (refereegranskat)abstract
- PURPOSE OF REVIEW: The omega-3 fatty acids (ω-3 FAs) docosahexaenoic acid and eicosapentaenoic acid are dietary components which have been ascribed many different health benefits. Inflammation is present in, and contributes to, pathological conditions in the central nervous system (CNS). Microglia are the primary cells with immune function in the CNS, and inflammation mediated by activated microglia is present in pathological conditions. In this review, we present and discuss findings on the modulation of microglial activities by ω-3 FAs in vivo as well as in vitro, and propose mechanisms for their effects.RECENT FINDINGS: The majority of studies show that ω-3 FAs have anti-inflammatory effects on microglia. However, phagocytosis is an activity associated with inflammation and is increased by ω-3 FAs. This can be understood in the light of recent research on the resolution of inflammation. Resolution is induced by proresolving factors, which are metabolites of ω-3 FAs. Proresolving factors are anti-inflammatory and have been shown to increase phagocytosis. Other mechanisms of the anti-inflammatory actions of ω-3 FAs involve the peroxisome proliferator-activated receptor-γ, ω-3 FA incorporation into the cell membrane, and inhibition of ion currents.SUMMARY: Immunomodulation by ω-3 FAs is mediated by several pathways that are interconnected and is a potential therapy for disorders in the CNS.
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| 33. |
- Hjorth, Erik, et al.
(författare)
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Omega-3 fatty acids enhance phagocytosis of Alzheimer's disease-related amyloid-β42 by human microglia and decrease inflammatory markers
- 2013
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Ingår i: Journal of Alzheimer's Disease. - : IOS Press. - 1387-2877 .- 1875-8908. ; 35:4, s. 697-713
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Tidskriftsartikel (refereegranskat)abstract
- The use of supplements with omega-3 (ω3) fatty acids (FAs) such as docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) is widespread due to proposed beneficial effects on the nervous and cardiovascular systems. Many effects of ω3 FAs are believed to be caused by down-regulation and resolution of inflammation. Alzheimer's disease (AD) is associated with inflammation mediated by microglia and astrocytes, and ω3 FAs have been proposed as potential treatments for AD. The focus of the present study is on the effects of DHA and EPA on microglial phagocytosis of the AD pathogen amyloid-β (Aβ), on secreted and cellular markers of immune activity, and on production of brain-derived neurotrophic factor (BDNF). Human CHME3 microglial cells were exposed to DHA or EPA, with or without the presence of Aβ42. Phagocytosis of Aβ42 was analyzed by flow cytometry in conjunction with immunocytochemistry using antibodies to cellular proteins. Secreted proteins were analyzed by ELISA. Both DHA and EPA were found to stimulate microglial phagocytosis of Aβ42. Phagocytosis of Aβ42 was performed by microglia with a predominance of M2 markers. EPA increased the levels of BDNF in the culture medium. The levels of TNF-α were decreased by DHA. Both DHA and EPA decreased the pro-inflammatory M1 markers CD40 and CD86, and DHA had a stimulatory effect on the anti-inflammatory M2 marker CD206. DHA and EPA can be beneficial in AD by enhancing removal of Aβ42, increasing neurotrophin production, decreasing pro-inflammatory cytokine production, and by inducing a shift in phenotype away from pro-inflammatory M1 activation.
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| 34. |
- Holmgren, Simon, et al.
(författare)
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Neuropsychiatric symptoms in dementia : a role for neuroinflammation?
- 2014
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Ingår i: Brain Research Bulletin. - : Elsevier. - 0361-9230 .- 1873-2747. ; 108, s. 88-93
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Tidskriftsartikel (refereegranskat)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.
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| 35. |
- Holmgren, Simon, et al.
(författare)
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Neuropsychiatric Symptoms in Dementia : Considering a Clinical Role for Electroencephalography
- 2022
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Ingår i: The Journal of Neuropsychiatry and Clinical Neurosciences. - : American Psychiatric Association Publishing, Inc.. - 0895-0172 .- 1545-7222. ; 34:3, s. 214-223
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Tidskriftsartikel (refereegranskat)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.
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| 36. |
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| 37. |
- Irving, Gerd Faxén, et al.
(författare)
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Omega-3 fatty acid supplementation effects on weight and appetite in patients with Alzheimer's disease : the omega-3 Alzheimer's disease study
- 2009
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Ingår i: Journal of The American Geriatrics Society. - : Wiley. - 0002-8614 .- 1532-5415. ; 57:1, s. 11-17
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To study the effects of omega (Omega)-3 fatty acid (FA) supplements on weight and appetite in patients with mild to moderate Alzheimer's disease (AD) in relation to inflammatory biomarkers and apolipoprotein E epsilon4 (APOEepsilon4). DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: Specialist memory clinics in the Stockholm catchment area. PARTICIPANTS: Two hundred four patients (aged 73+/-9, 52% women) with mild to moderate AD. INTERVENTION: Patients with AD received 1.7 g of docosahexaenoic acid (DHA) and 0.6 g of eicosapentaenoic acid (EPA) (Omega-3/Omega-3 group; n=89, aged 73+/-9, 57% women) or placebo 0.6 g of linoleic acid per day (placebo/Omega-3 group; n=85, aged 73+/-9, 46% women) for 6 months. After 6 months, all patients received DHA and EPA for another 6 months. MEASUREMENTS: Anthropometry, biochemical nutritional and inflammatory markers, and appetite assessed by caregiver. RESULTS: Mean weight and body mass index (kg/m(2)) at baseline were 70.0+/-11.8 kg and 24.3+/-3.0 kg/m(2), respectively. At 6- and 12-month follow-up, weight had increased 0.7+/-2.5 kg (P=.02) and 1.4+/-2.9 kg (P<.001) in the Omega-3/Omega-3 group. In the placebo group, weight was unchanged at 6 months but had increased (P=.01) at 12 months follow-up after Omega-3 supplementation was initiated. Appetite improved in the Omega-3/Omega-3 group over the treatment period (P=.01). In logistic regression analyses, not carrying the APOEepsilon4 allele and high plasma DHA concentrations were independently related to weight gain in the combined group of patients at 6 months follow-up. CONCLUSION: A DHA-enriched Omega-3 FA supplement may positively affect weight and appetite in patients with mild to moderate AD. Not carrying the APOEepsilon4 allele and high DHA were independently associated with weight gain.
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| 38. |
- Jansen, Willemijn J, et al.
(författare)
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Association of Cerebral Amyloid-β Aggregation With Cognitive Functioning in Persons Without Dementia.
- 2018
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Ingår i: JAMA psychiatry. - : American Medical Association (AMA). - 2168-6238 .- 2168-622X. ; 75:1, s. 84-95
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Tidskriftsartikel (refereegranskat)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.
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| 39. |
- Jansen, Willemijn J, et al.
(författare)
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Prevalence Estimates of Amyloid Abnormality Across the Alzheimer Disease Clinical Spectrum.
- 2022
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Ingår i: JAMA neurology. - : American Medical Association (AMA). - 2168-6157 .- 2168-6149. ; 79:3, s. 228-243
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Tidskriftsartikel (refereegranskat)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 19 097 participants (mean [SD] age, 69.1 [9.8] years; 10 148 women [53.1%]) included, 10 139 (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.
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| 40. |
- Jansen, Willemijn J, et al.
(författare)
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Prevalence of cerebral amyloid pathology in persons without dementia: a meta-analysis.
- 2015
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Ingår i: JAMA. - : American Medical Association (AMA). - 1538-3598 .- 0098-7484. ; 313:19, s. 1924-38
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Tidskriftsartikel (refereegranskat)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.
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