scholarly journals Higher baseline levels of CSF inflammation increase risk of incident mild cognitive impairment and Alzheimer’s disease dementia

Author(s):  
Joey Annette Contreras ◽  
Vahan Aslanyan ◽  
Daniel S Albrecht ◽  
Wendy J. Mack ◽  
Judy Pa

Abstract Background Few studies have investigated how inflammation early in the disease course may affect AD progression over time despite converging evidence that elevated levels of inflammation are associated with AD in cross-sectional studies. Methods Two-hundred ninety-two research participants with CSF biomarkers from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) were included in this study. Cox proportional hazards models were used to investigate whether baseline levels of inflammatory CSF markers were associated with incident mild cognitive impairment or AD and time to conversion. Potential moderating effects of sex and APOE4 were also examined. Results Elevated levels of pro-inflammatory markers TNF-α, IL-9, and IL-12p40 at baseline were associated with higher rates of conversion to MCI/AD. Interactions with sex and APOE4 were observed, such that women with elevated TNF- α and all APOE4 carriers with elevated IL-9 levels had shorter times to conversion. Additionally, TNF-α mediated the relationship between elevated IL-12p40 and IL-9. Conclusion Elevated inflammation markers are associated with incident MCI or AD, and the factors of sex and APOE4 status modify the time to conversion.

2009 ◽  
Vol 5 (4S_Part_13) ◽  
pp. P383-P383
Author(s):  
Simon Forstmeier ◽  
Michael Wagner ◽  
Wolfgang Maier ◽  
Hendrik Van Den Bussche ◽  
Birgitt Wiese ◽  
...  

2019 ◽  
Author(s):  
Jae Woo Choi ◽  
Kang Soo Lee ◽  
Euna Han

Abstract Background This study aims to investigate suicide risk within one year of receiving a diagnosis of cognitive impairment in older adults without mental disorders. Methods This study used National Health Insurance Service-Senior Cohort data on older adults with newly diagnosed cognitive impairment including Alzheimer’s disease, vascular dementia, other/unspecified dementia, and mild cognitive impairment from 2004 to 2012. We selected 41,195 older adults without cognitive impairment through 1:1 propensity score matching using age, gender, Charlson Comorbidity Index, and index year, with follow-up throughout 2013. We eliminated subjects with mental disorders and estimated adjusted hazard ratios (AHR) of suicide deaths within one year after diagnosis using the Cox proportional hazards models. Results We identified 49 suicide deaths during the first year after cognitive impairment diagnosis. The proportion of observed suicide deaths was the highest within one year after cognitive impairment diagnosis (48.5% of total); older adults with cognitive impairment were at a higher suicide risk than those without cognitive impairment (AHR, 1.89; 95% confidence interval [CI], 1.18–3.04). Subjects with Alzheimer’s disease and other/unspecified dementia were at greater suicide risk than those without cognitive impairment (AHR, 1.94, 1.94; 95% CI, 1.12–3.38, 1.05–3.58). Suicide risk in female and young-old adults (60–74 years) with cognitive impairment was higher than in the comparison group (AHR, 2.61, 5.13; 95% CI, 1.29–5.28, 1.48–17.82). Conclusions Older patients with cognitive impairment were at increased suicide risk within one year of diagnosis. Early intervention for suicide prevention should be provided to older adults with cognitive impairment.


2020 ◽  
Vol 77 (2) ◽  
pp. 843-853
Author(s):  
Antoine R. Trammell ◽  
Darius J. McDaniel ◽  
Malik Obideen ◽  
Maureen Okafor ◽  
Tiffany L. Thomas ◽  
...  

Background: African Americans (AA) have a higher Alzheimer’s disease (AD) prevalence and report more perceived stress than White Americans. The biological basis of the stress-AD link is unclear. This study investigates the connection between stress and AD biomarkers in a biracial cohort. Objective: Establish biomarker evidence for the observed association between stress and AD, especially in AA. Methods: A cross-sectional study (n = 364, 41.8% AA) administering cognitive tests and the perceived stress scale (PSS) questionnaire. A subset (n = 309) provided cerebrospinal fluid for measurement of Aβ42, Tau, Ptau, Tau/Aβ42 (TAR), and Ptau/Aβ42 (PTAR). Multivariate linear regression, including factors that confound racial differences in AD, was performed. Results: Higher PSS scores were associated with higher Ptau (β= 0.43, p = 0.01) and PTAR (β= 0.005, p = 0.03) in AA with impaired cognition (mild cognitive impairment). Conclusion: Higher PSS scores were associated with Tau-related AD biomarker indices in AA/MCI, suggesting a potential biological connection for stress with AD and its racial disparity.


SLEEP ◽  
2020 ◽  
Vol 43 (Supplement_1) ◽  
pp. A23-A23
Author(s):  
R Mehra ◽  
R Bhambra ◽  
J Bena ◽  
L Bekris ◽  
J Leverenz ◽  
...  

Abstract Introduction Although recent data implicates sleep and circadian disruption to neurodegeneration in Alzheimer’s Disease (AD), the association of objective circadian biomarkers and neurodegeneration remains understudied. We hypothesize that actigraphy-based circadian measures are associated with cerebrospinal fluid (CSF) biomarkers of neurodegeneration in those mild cognitive impairment due to AD (MCI-AD). Methods Eighteen patients with CSF biomarker-confirmed MCI-AD underwent actigraphy monitoring generating the following circadian measures: amplitude, F-ratio and mesor and morning collection of CSF biomarkers of neurodegeneration (Aβ42,t-tau,p-tau). Linear models were used to evaluate the association of circadian and CSF measures; logarithmic transformations were performed on neurodegenerative markers for greater normality. Analysis was performed using SAS software. A significance level of 0.05 was assumed for all tests. Results Eighteen MCI-AD patients who were 68± 6.2 years, 44% female, with median AHI=12 and underwent actigraphy monitoring for 8.2+/-3.2 days were included. There was no significant association of circadian measures and Aβ42 nor with mesor and neurodegeneration biomarkers. Amplitude was associated with both p-tau and t-tau, such that each 10 unit increase in amplitude resulted in a predicted increase in p-tau of 8% (95% CI:1%-15%, p=0.018) and an increase of 13% (3%-23%; p=0.01) in t-tau. F-ratio was positively associated with p-tau and t-tau; each 1000 unit increase in F-ratio resulted in a predicted 12% (4%-22%; p=0.007) increase in P-tau and 20%(6%-35%; p=0.005) increase in t-tau. Associations of these circadian measures and CSF levels of p-tau and t-tau remained statistically significant after adjustment for age and sex. Conclusion Among patients with symptomatic MCI stages of AD, objective measures of circadian rhythm disruption are associated with CSF-based biomarkers of neurodegeneration even after consideration of age and sex. Future investigation should clarify directionality of this association and potential utility of circadian-based interventions in the mitigation of AD progression. Support N/A


2020 ◽  
Vol 131 ◽  
pp. 110816 ◽  
Author(s):  
Felipe de Oliveira Silva ◽  
José Vinícius Ferreira ◽  
Jéssica Plácido ◽  
Daniel Chagas ◽  
Jomilto Praxedes ◽  
...  

2017 ◽  
Vol 30 (1) ◽  
pp. 103-113 ◽  
Author(s):  
N. Siafarikas ◽  
G. Selbaek ◽  
T. Fladby ◽  
J. Šaltytė Benth ◽  
E. Auning ◽  
...  

ABSTRACTBackground:Neuropsychiatric symptoms (NPS), such as depression, apathy, agitation, and psychotic symptoms are common in mild cognitive impairment (MCI) and dementia in Alzheimer's disease (AD). Subgroups of NPS have been reported. Yet the relationship of NPS and their subgroups to different stages of cognitive impairment is unclear. Most previous studies are based on small sample sizes and show conflicting results. We sought to examine the frequency of NPS and their subgroups in MCI and different stages of dementia in AD.Methods:This was a cross-sectional study using data from a Norwegian national registry of memory clinics. From a total sample of 4,571 patients, we included those with MCI or AD (MCI 817, mild AD 883, moderate–severe AD 441). To compare variables across groups ANOVA or χ2-test was applied. We used factor analysis of Neuropsychiatric Inventory Questionnaire (NPI-Q) items to identify subgroups of NPS.Results:The frequency of any NPS was 87.2% (AD 91.2%, MCI 79.5%; p < 0.001) and increased with increasing severity of cognitive decline. The most frequent NPS in MCI was depression. Apathy was the most frequent NPS in AD across different stages of severity. The factor analysis identified three subgroups in MCI and mild AD, and a fourth one in moderate–severe AD. We labelled the subgroups “depression,” “agitation,” “psychosis,” and “elation.”Conclusions:The frequency of NPS is high in MCI and AD and increases with the severity of cognitive decline. The subgroups of NPS were relatively consistent from MCI to moderate-severe AD. The subgroup elation appeared only in moderate-severe AD.


2021 ◽  
Author(s):  
Yu-Kai Lin ◽  
Chih-Sung Liang ◽  
Chia-Kuang Tsai ◽  
Chia-Lin Tsai ◽  
Jiunn-Tay Lee ◽  
...  

Abstract BACKGROUND Alzheimer’s disease (AD) involves the abnormal activity of transition metals and metal ion dyshomeostasis. The present study aimed to assess the potential of 36 trace elements in predicting cognitive decline in patients with amnestic mild cognitive impairment (aMCI) or AD. METHODS All participants (controls, aMCI, and AD) underwent baseline cognitive tests, which included the Mini-Mental State Examination (MMSE) and plasma biomarker examinations. We conducted a trend analysis for the cognitive tests and plasma trace elements and examined the correlations between the latter and annual MMSE changes during follow-up. RESULTS An increase in the disease severity was linked to lowered boron (B), bismuth (Bi), thorium (Th), and uranium (U) plasma concentrations (adjusted P < 0.05). “B”, mercury (Hg) and “Th” levels could detect different cognitive stages. “B” displayed high area under the receiver operating characteristic curves (AUCs) for aMCI and AD versus controls (97.6%, cut-off value: ≤73.1 ug/l and 100%, cut-off value: ≤47.1 ug/l, respectively). “Hg” displayed the highest AUC result to differentiate AD from aMCI (79.9%, cut-off value: ≤1.02 ug/l). Higher baseline levels of calcium (r = 0.50, p = 0.026) were associated with less annual cognitive decline. While higher baseline levels of “B” (r=-0.70, p = 0.001), zirconium (r=-0.58, p = 0.007), “Th” (r=-0.52, p = 0.020) were associated with rapid annual cognitive decline in the aMCI group, those of manganese (r=-0.91, p = 0.035) were associated with rapid annual cognitive decline in the AD group. CONCLUSION Plasma metal level biomarkers can be used as an in vivo tool to study and identify patients with aMCI and AD.


2022 ◽  
Author(s):  
Fernanda Hansen Pacheco de Moraes ◽  
Felipe Sudo ◽  
Marina Monteiro Carneiro ◽  
Bruno R. P. de Melo ◽  
Paulo Mattos ◽  
...  

This manuscript presents a study with recruited volunteers that comprehends three sorts of events present in Alzheimer's Disease (AD) evolution (structural, biochemical, and cognitive) to propose an update in neurodegeneration biomarkers for AD. The novel variables, K, I, and S, suggested based on physics properties and empirical evidence, are defined by power-law relations between cortical thickness, exposed and total area, and natural descriptors of brain morphology. Our central hypothesis is that variable K, almost constant in healthy human subjects, is a better discriminator of a diseased brain than the current morphological biomarker, Cortical Thickness, due to its aggregated information. We extracted morphological features from 3T MRI T1w images of 123 elderly subjects: 77 Healthy Cognitive Unimpaired Controls (CTL), 33 Mild Cognitive Impairment (MCI) patients, and 13 Alzheimer's Disease (AD) patients. Moreover, Cerebrospinal Fluid (CSF) biomarkers and clinical data scores were correlated with K, intending to characterize health and disease in the cortex with morphological criteria and cognitive-behavioral profiles. K distinguishes Alzheimer's Disease, Mild Cognitive Impairment, and Healthy Cognitive Unimpaired Controls globally and locally with reasonable accuracy (CTL-AD, 0.82; CTL-MCI, 0.58). Correlations were found between global and local K associated with clinical behavioral data (executive function and memory assessments) and CSF biomarkers (t-Tau, Aβ-40, and Aβ-42). The results suggest that the cortical folding component, K, is a premature discriminator of healthy aging, Mild Cognitive Impairment, and Alzheimer's Disease, with significant differences within diagnostics. Despite the non-concomitant events, we found correlations between brain structural degeneration (K), cognitive tasks, and biochemical markers.


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