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- Kern, Silke, et al.
(author)
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Lower CSF interleukin-6 predicts future depression in a population-based sample of older women followed for 17 years
- 2013
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In: Brain Behavior and Immunity. - : Elsevier BV. - 0889-1591. ; 32, s. 153-158
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Journal article (peer-reviewed)abstract
- Objective The literature regarding cerebrospinal fluid (CSF) cytokines in geriatric depression is sparse. The aim of this study was to examine associations between CSF interleukin-6 (IL-6) and related proinflammatory cytokines and current and future depression in a population-based sample of older women who were followed for 17 years. Methods 83 non-demented women aged 70–84 years who participated in the Prospective Population Study of Women in Gothenburg, Sweden took part in a lumbar puncture in 1992–3. CSF- IL-6, interleukin-1β (IL-1β), interleukin- 8 (IL-8) and tumor necrosis factor-α (TNF-α) were measured. Psychiatric symptoms were rated with the Comprehensive Psychopathological Rating Scale at baseline and at three subsequent face-to-face examinations. Depression (major or minor) was diagnosed in accordance with DSM-IV/DSM-IV research criteria. Results At baseline, women with ongoing depression had lower levels of IL-6 (p < 0.04), IL-8 (p < 0.05) and TNF-α (p < 0.05) compared with those without depression. In women without depression at baseline, lower CSF IL-6 levels predicted depression at one or more follow-up examination (p < 0.03). Results from the generalized linear mixed logistic model using all baseline and follow-up data on depression status and Mini Mental State Examination score showed a significant relationship between IL-6 and depression (p = 0.005 OR 0.370 CI [0.184–0.744]). Conclusion Lower levels of CSF IL-6 were associated with current depression and with future depression during a follow-up of almost two decades. Our findings suggest that lower levels of CSF IL-6 may be related to depression vulnerability in later life.
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| 4. |
- Abdullah, Laila, et al.
(author)
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The Influence of Baseline Alzheimer's Disease Severity on Cognitive Decline and CSF Biomarkers in the NILVAD Trial.
- 2020
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In: Frontiers in neurology. - : Frontiers Media SA. - 1664-2295. ; 11
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Journal article (peer-reviewed)abstract
- We examined the effects of a dihydropyridine calcium channel blocker nilvadipine with anti-inflammatory properties on cognition and cerebrospinal fluid (CSF) biomarkers by baseline Alzheimer's disease (AD) severity. Exploratory analyses were performed on the dataset (n = 497) of a phase III randomized placebo-controlled trial to examine the response to nilvadipine in AD subjects stratified by baseline AD severity into very mild (MMSE ≥ 25), mild (MMSE 20-24) and moderate AD (MMSE < 20). The outcome measures included total and subscale scores of the Alzheimer's Disease Assessment Scale Cognitive 12 (ADAS-Cog 12), the Clinical Dementia Rating Scale sum of boxes (CDR-sb) and the AD composite score (ADCOMS). Cerebrospinal fluid biomarkers Aβ38, Aβ40, Aβ42, neurofilament light chain (NFL), neurogranin, YKL-40, total tau and P181 tau (ptau) were measured in a subset of samples (n = 55). Regression analyses were adjusted for confounders to specifically examine the influence of nilvadipine and baseline AD severity on cognitive outcomes over 78-weeks. Compared to their respective placebo-controls, nilvadipine-treated, very mild AD subjects showed less decline, whereas moderate AD subjects showed a greater cognitive decline on the ADAS-Cog 12 test and the ADCOMS. A lower decline was observed after nilvadipine treatment for a composite memory trait in very mild AD subjects and a composite language trait in mild AD subjects. Cerebrospinal fluid Aβ42/Aβ40 ratios were increased in mild AD and decreased in moderate AD patients treated with nilvadipine, compared to their respective controls. Among moderate AD subjects, levels of ptau, total tau, neurogranin and YKL-40 increased in subjects treated with nilvadipine compared to placebo. These studies suggest that baseline AD severity influenced the treatment outcome in the NILVAD trial and that future clinical trials of nilvadipine should be restricted to mild and very mild AD patients. Trial Registration: NCT02017340 Registered 20 December 2013, https://clinicaltrials.gov/ct2/show/NCT02017340 EUDRACT Reference Number 2012-002764-27 Registered 04 February 2013, https://www.clinicaltrialsregister.eu/ctr-search/search?query=2012-002764-27.
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| 5. |
- Bjerke, Maria, 1977, et al.
(author)
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Cerebrospinal Fluid Fatty Acid-Binding Protein 3 is Related to Dementia Development in a Population-Based Sample of Older Adult Women Followed for 8 Years.
- 2016
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In: Journal of Alzheimer's disease : JAD. - 1875-8908. ; 49:3, s. 733-741
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Journal article (peer-reviewed)abstract
- BACKGROUND: Increased fatty acid-binding protein 3 (FABP-3) levels have been reported in neurodegenerative diseases, including Alzheimer's disease (AD). Cerebrospinal fluid (CSF) FABP-3 has therefore been proposed as a putative marker for dementia. Population-based studies examining whether CSF FABP-3 predicts later development of dementia are lacking. OBJECTIVE: The aim of this study was to examine CSF levels of FABP-3 in relation to later development of dementia in elderly women and in relation to Aβ42, T-tau, P-tau181, and CSF: serum albumin ratio. METHODS: 86 non-demented women aged 70-84 years who participated in the Prospective Population Study of Women in Gothenburg, Sweden took part in a lumbar puncture in 1992-93. CSF-FABP-3, Aβ42, T-tau, P-tau181, and the CSF: serum albumin ratio were measured at baseline. Participants were examined with a neuropsychiatric exam at baseline and at follow-up in 2000. Dementia was diagnosed in accordance with DSM-III-R criteria. RESULTS: Between 1992 and 2000, 8 women developed dementia (4 AD, 3 vascular dementia, 1 mixed vascular dementia and AD). Higher levels of CSF-FABP-3 at baseline were related to development of dementia (OR 1.36 CI [1.05-1.76] p = 0.022) and the subtype AD (OR 1.38 CI [1.06-1.82), p = 0.019) during follow-up. FABP-3 correlated with CSF T-tau (r = 0.88, p < 0.001), P-tau181 (r = 0.619, p < 0.001), and CSF:serum albumin ratio (r = 0.233, p = 0.031), but not with Aβ42 (r = -0.08, p = 0.444)Conclusion: CSF FABP-3 may be an early marker for later development of dementia, probably related to neuronal degeneration, but independent of Aβ metabolism.
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- Höglund, Kina, 1976, et al.
(author)
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Preclinical amyloid pathology biomarker positivity: effects on tau pathology and neurodegeneration
- 2017
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In: Translational Psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 7
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Journal article (peer-reviewed)abstract
- Brain autopsy and biomarker studies indicate that the pathology of Alzheimer's disease (AD) is initiated at least 10-20 years before clinical symptoms. This provides a window of opportunity to initiate preventive treatment. However, this emphasizes the necessity for biomarkers that identify individuals at risk for developing AD later in life. In this cross-sectional study, originating from three epidemiologic studies in Sweden (n = 1428), the objective was to examine whether amyloid pathology, as determined by low cerebrospinal fluid (CSF) concentration of the 42 amino acid form of beta-amyloid (A beta 42), is associated with biomarker evidence of other pathological changes in cognitively healthy elderly. A total of 129 patients were included and CSF levels of A beta 42, total tau, tau phosphorylated at threonine 181 (p-tau), neurogranin, VILIP-1, VEGF, FABP3, A beta 40, neurofilament light, MBP, orexin A, BDNF and YKL-40 were measured. Among these healthy elderly, 35.6% (N=46) had CSF A beta 42 levels below 530 pg ml(-1). These individuals displayed significantly higher CSF concentrations of t-tau (P < 0.001), p-tau (181) (P < 0.001), neurogranin (P = 0.009) and FABP3 (P = 0.044) compared with amyloid-negative individuals. Our study indicates that there is a subpopulation among healthy older individuals who have amyloid pathology along with signs of ongoing neuronal and synaptic degeneration, as well as tangle pathology. Previous studies have demonstrated that increase in CSF tau and p-tau is a specific sign of AD progression that occurs downstream of the deposition of A beta. On the basis of this, our data suggest that these subjects are at risk for developing AD. We also confirm the association between APOE epsilon 4 and amyloid pathology in healthy older individuals.
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- Kern, Silke, et al.
(author)
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Prevalence of preclinical Alzheimer disease Comparison of current classification systems
- 2018
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In: Neurology. - : Ovid Technologies (Wolters Kluwer Health). - 0028-3878 .- 1526-632X. ; 90:19, s. E1682-E1691
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Journal article (peer-reviewed)abstract
- Objective To determine the prevalence of preclinical Alzheimer disease (AD) according to current classification systems by examining CSF from a representative general population sample of 70-year-olds from Gothenburg, Sweden. The sample was derived from the population-based H70 Gothenburg Birth Cohort Studies in Gothenburg, Sweden. The participants (n = 322, age 70 years) underwent comprehensive neuropsychiatric, cognitive, and somatic examinations. CSF levels of beta-amyloid (A beta)(42), A beta(40), total tau, and phosphorylated tau were measured. Preclinical AD was classified according to criteria of the A/T/N system, Dubois 2016, National Institute on Aging-Alzheimer's Association (NIA-AA) criteria, and International Working Group-2 (IWG-2) criteria. Individuals with Clinical Dementia Rating score > 0 were excluded, leaving 259 cognitively unimpaired individuals. The prevalence of amyloid pathology was 22.8%, of total tau pathology was 33.2%, and of phosphorylated tau pathology was 6.9%. With the A/T/N system, the prevalence of A+/T-/N- was 13.1%, A+/T-/N+ was 7.3%, A+/T+/N+ was 2.3%, A-/T-/N+ was 18.9%, and A-/T+/N+ was 4.6%. When the Dubois criteria were applied, the prevalence of asymptomatic at risk for AD was 36.7% and of preclinical AD was 9.7%. With the NIA-AA criteria, the prevalence of stage 1 was 13.1% and stage 2 was 9.7%. With the IWG-2 criteria, the prevalence of asymptomatic at risk for AD was 9.7%. The APOE epsilon 4 allele was associated with several of the categories. Men more often had total tau pathology, A+/T-/N+, preclinical AD according to Dubois 2016, asymptomatic at risk for AD according to the IWG-2 criteria, and NIA-AA stage 2. The prevalence of pathologic AD markers was very common (46%) in a representative population sample of 70-year-olds. The clinical implications of these findings need to be scrutinized further in longitudinal studies.
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