A Mixed-Effects Model of Associations between Interleukin-6 and Hippocampal Volume

2021 ◽  
Author(s):  
Erin R Harrell ◽  
Chuong Bui ◽  
Sharlene D Newman ◽  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Interleukin 6 ◽  
Mixed Models ◽  
Allostatic Load ◽  
Mmse Score ◽  
Hippocampal Volume ◽  
Within Subjects ◽  
Normative Aging ◽  
The Relationship

Abstract Previous studies report hippocampal volume loss can help predict conversion from normative aging to mild cognitive impairment (MCI) to dementia. Additionally, a growing literature indicates that stress-related allostatic load may increase disease vulnerability. The current study examined the relationship between stress related cytokines (i.e., interleukin-6 - IL-6), cognition as measured by Mini Mental Status scores (MMSE), and hippocampal volume. Mixed-models were employed to examine both within (across time) and between subjects effects of IL-6 and hippocampal volume on MMSE score among 566 participants from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). The within subjects analysis found left hippocampal volume significantly (p= .009) predicted MMSE score. Between subjects analysis found the effect of IL-6 on MMSE was moderated by right hippocampal volume (p = .001). These results replicate previous findings and also extend prior work demonstrating stress-related cytokines may play a role in Alzheimer’s disease (AD) progression.

Abstract T P160: Influence of Polyunsaturated Fatty Acids on Cognition in Elderly Alzheimer's Disease Patients

Stroke ◽  
2015 ◽  
Vol 46 (suppl_1) ◽  
Author(s):  
Takashi Yamazaki ◽  
Ken Nagata ◽  
Daiki Takano ◽  
Tetsuya Maeda
Keyword(s):  
Alzheimer’S Disease ◽  
Blood Pressure ◽  
Alzheimer's Disease ◽  
Cognitive Function ◽  
Mmse Score ◽  
Characteristic Curve ◽  
Follow Up Study ◽  
Cognitive Stability ◽  
The Relationship

Background: Many genes and environmental factors linked to Alzheimer’s disease (AD) risk affect lipid metabolism or the cardiovascular system, strongly implicating cerebrovascular and metabolic dysfunction in AD pathogenesis. Although some PUFAs may improve cognitive function in aging individuals, it is still unclear how different PUFAs influence AD neuropathology and cognitive function. Objective: To examine the influence of polyunsaturated fatty acid (PUFA) metabolism on AD-associated cognitive decline, we investigated the relationship between serum PUFA profile and neuropsychological test performance. Methods: Cognitive functioning in patients with probable AD (n = 174, mean age 77.6 years) was examined using the Mini-Mental State Exam (MMSE) and clock drawing test (CDT). Serum samples were obtained for PUFA profile, including the eicosapentaenoic acid/arachidonic acid (EPA/AA) ratio, and measurement of brain natriuretic peptide (BNP) concentration. In the follow-up study, 47 subjects repeated MMSE and CDT after 1 year, According to the second MMSE score, the subjects were divided into the following 2 groups: those with unchanged or improved MMSE score and those with lower MMSE score. A receiver operating characteristic curve was used to evaluate the relationship between the EPA/AA ratio and 1-year cognitive stability. Results: In the cross-sectional study, total MMSE score correlated positively with the EPA/AA ratio and systolic blood pressure (SBP), and negatively with age and diastolic blood pressure (DBP) (p < 0.05). In the follow-up study, the MMSE score was lower than baseline in 20 subjects, whereas it was improved or unchanged in 29 patients. The EPA/AA ratio in the stable group was significantly greater than that in the deteriorating group, suggesting an association between higher EPA/AA ratio and cognitive stability over 1 year. The EPA/AA ratio predicted stability of cognitive performance with a sensitivity of 66% and specificity of 70% (odds ratio = 4.43) when the cut-off was 0.67. Conclusion: Our results suggest that serum EPA concentration strongly influences cognitive performances in AD patients. The EPA/AA ratio was a sensitive indicator of cognitive stability in this patient group.

scholarly journals Different Temporal Patterns of Specific and General Autobiographical Memories across the Lifespan in Alzheimer’s Disease

2015 ◽  
Vol 2015 ◽  
pp. 1-14 ◽  
Author(s):  
Nathalie Philippi ◽  
François Rousseau ◽  
Vincent Noblet ◽  
Anne Botzung ◽  
Olivier Després ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Temporal Lobe ◽  
Temporal Cortex ◽  
Temporal Patterns ◽  
Hippocampal Volume ◽  
Autobiographical Memories ◽  
Temporal Gradient ◽  
Repeated Events ◽  
The Relationship

We compared specific (i.e., associated with a unique time and space) and general (i.e., extended or repeated events) autobiographical memories (AbM) in Alzheimer’s disease (AD). The comparison aims at investigating the relationship between these two components of AbM across the lifespan and the volume of cerebral regions of interest within the temporal lobe. We hypothesized that the ability to elicit specific memories would correlate with hippocampal volume, whereas evoking general memories would be related to lateral temporal lobe. AbM was assessed using the modified Crovitz test in 18 patients with early AD and 18 matched controls. The proportions of total memories—supposed to reflect the ability to produce general memories—and specific memories retrieved were compared between AD patients and controls. Correlations to MRI volumes of temporal cortex were tested. We found different temporal patterns for specific and general memories in AD patients, with (i) relatively spared general memories, according to a temporal gradient that preserved remote memories, predominantly associated with right lateral temporal cortex volume. (ii) Conversely, the retrieval of specific AbMs was impaired for all life periods and correlated with bilateral hippocampal volumes. Our results highlight a shift from an initially episodic to a semantic nature of AbMs during AD, where the abstracted form of memories remains.

scholarly journals CORRELATION BETWEEN COGNITION AND FUNCTION ACROSS THE SPECTRUM OF ALZHEIMER’S DISEASE

2016 ◽  
pp. 1-7
Author(s):  
H. Liu-Seifert ◽  
E. Siemers ◽  
K. Selzler ◽  
K. Sundell ◽  
P. Aisen ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Disease Progression ◽  
Mmse Score ◽  
Disease Stage ◽  
Two Phase ◽  
Identity Studies ◽  
Moderate Dementia ◽  
And Function ◽  
The Relationship

Background: Both cognitive and functional deterioration are characteristic of the clinical progression of Alzheimer’s disease (AD). Objectives: To systematically assess correlations between widely used measures of cognition and function across the spectrum of AD. Design: Spearman rank correlations were calculated for cognitive and functional measures across datasets from various AD patient populations. Setting: Post-hoc analysis from existing databases. Participants: Pooled data from placebo-treated patients with mild (MMSE score ≥20 and ≤26) and moderate (MMSE score ≥16 and ≤19) AD dementia from two Phase 3 solanezumab (EXPEDITION/2) and two semagecesatat (IDENTITY/2) studies and normal, late mild cognitive impairment (LMCI) and mild AD patients from the Alzheimer’s Disease Neuroimaging Initiative 2-Grand Opportunity (ADNI-2/GO). Intervention (if any): Placebo (EXPEDITION/2 and IDENTITY/2 subjects) Measurements: Cognitive and functional abilities were measured in all datasets. Data were collected at baseline and every three months for 18 months in EXPEDITION and IDENTITY studies; and at baseline, 6, 12, and 24 months in the ADNI dataset. Results: The relationship of cognition and function became stronger over time as AD patients progressed from preclinical to moderate dementia disease stages, with the magnitude of correlations dependent on disease stage and the complexity of functional task. The correlations were minimal in the normal control population, but became stronger with disease progression. Conclusions: This analysis found that measures of cognition and function become more strongly correlated with disease progression from preclinical to moderate dementia across multiple datasets. These findings improve the understanding of the relationship between cognitive and functional clinical measures during the course of AD progression and how cognition and function measures relate to each other in AD clinical trials.

scholarly journals Does Informant-Based Reporting of Cognitive Decline Correlate with Age-Adjusted Hippocampal Volume in Mild Cognitive Impairment and Alzheimer’s Disease?

2021 ◽  
Vol 5 (1) ◽  
pp. 207-211
Author(s):  
Marwan Sabbagh ◽  
Justin Miller ◽  
Stephen Jones ◽  
Aaron Ritter ◽  
Jiong Shi ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Cognitive Decline ◽  
Hippocampal Volume ◽  
Screening Tools ◽  
Functional Impairments ◽  
Diagnostic Status ◽  
The Relationship

Background: Informant-based measures are effective screening tools for cognitive impairment. The Alzheimer’s Questionnaire (AQ) is a subjective, informant-based measure that detects amnestic mild cognitive impairment (aMCI) and Alzheimer’s disease (AD) with high sensitivity and specificity and has been shown to predict amyloid burden. Objective: To determine whether informant-based report of cognitive decline correlates with hippocampal volume changes in MCI and AD. Methods: Retrospective chart review of 139 clinically referred patients with clinical diagnoses of aMCI or mild dementia due to AD was conducted. Diagnostic status (clinical diagnosis made by a neurologist), NeuroQuant measured MRI brain with percentile rank hippocampal volume, Montreal Cognitive Assessment (MoCA) total, AQ-Total score, and demographic variables were extracted from medical records. Spearman correlation was used to assess the relationship between hippocampal volume and AQ-Total. The AQ was used to assign diagnostic status. Thus, the relationship between the AQ and diagnostic status was excluded. Results: The sample include 88 female and 51 male participants. The mean age was 74.37±9.45, mean MOCA was 22.65±4.18, mean education was 14.80±3.35, and mean AQ score was 10.54±5.22. Hippocampal volume and the AQ correlation was r = –0.33 [95%CI –0.47 to –0.17], p < 0.0001. Conclusion: In a mixed-clinical sample of patients presenting to an outpatient memory disorders center, higher endorseme-nts of functional impairments by caregivers were significantly associated with smaller hippocampal volumes. When used in conjunction with other available measures, these findings further support the role of the AQ in clinical decision-making and demonstrate an additional relationship between clinical measures and volumetric MRI.

scholarly journals Age, vascular disease, and Alzheimer’s disease pathologies in amyloid negative elderly adults

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Tengfei Guo ◽  
Susan M. Landau ◽  
William J. Jagust ◽  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Decline ◽  
Fdg Pet ◽  
Amyloid Β ◽  
Hippocampal Volume ◽  
Factors Associated ◽  
Male Sex ◽  
The Relationship

Abstract Background We recently reported that CSF phosphorylated tau (p-Tau181) relative to Aβ40 (CSF p-Tau/Aβ40 ratio) was less noisy and increased associations with Alzheimer’s disease (AD) biomarkers compared to CSF p-Tau181 alone. While elevations of CSF p-Tau/Aβ40 can occur in amyloid-β (Aβ) negative (Aβ-) individuals, the factors associated with these elevations and their role in neurodegeneration and cognitive decline are unknown. We aim to explore factors associated with elevated tau in CSF, and how these elevated tau are related to neurodegeneration and cognitive decline in the absence of Aβ positivity. Methods We examined relationships between CSF p-Tau/Aβ40, and CSF Aβ42/Aβ40, Aβ PET, and white matter hyperintensities (WMH) as well as vascular risk factors in 149 cognitively unimpaired and 52 impaired individuals who were presumably not on the Alzheimer’s disease (AD) pathway due to negative Aβ status on both CSF and PET. Subgroups had 18F-fluorodeoxyglucose (FDG) PET and adjusted hippocampal volume (aHCV), and longitudinal measures of CSF, aHCV, FDG PET, and cognition data, so we examined CSF p-Tau/Aβ40 associations with these measures as well. Results Elevated CSF p-Tau/Aβ40 was associated with older age, male sex, greater WMH, and hypertension as well as a pattern of hippocampal atrophy and temporoparietal hypometabolism characteristic of AD. Lower CSF Aβ42/Aβ40, higher WMH, and hypertension but not age, sex, Aβ PET, APOE-ε4 status, body mass index, smoking, and hyperlipidemia at baseline predicted CSF p-Tau/Aβ40 increases over approximately 5 years of follow-up. The relationship between CSF p-Tau/Aβ40 and subsequent cognitive decline was partially or fully explained by neurodegenerative measurements. Conclusions These data provide surprising clues as to the etiology and significance of tau pathology in the absence of Aβ. It seems likely that, in addition to age, both cerebrovascular disease and subthreshold levels of Aβ are related to this tau accumulation. Crucially, this phenotype of CSF tau elevation in amyloid-negative individuals share features with AD such as a pattern of metabolic decline and regional brain atrophy.

MiR-335-5p Inhibits β-Amyloid (Aβ) Accumulation to Attenuate Cognitive Deficits Through Targeting c-jun-N-terminal Kinase 3 in Alzheimer’s Disease

2020 ◽  
Vol 17 (1) ◽  
pp. 93-101 ◽  
Author(s):  
Dan Wang ◽  
Zhifu Fei ◽  
Song Luo ◽  
Hai Wang
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Transgenic Mice ◽  
Western Blot ◽  
Mrna Expression ◽  
Cognitive Deficits ◽  
Protein Levels ◽  
Amyloid Aβ ◽  
Β Amyloid ◽  
The Relationship

Objectives: Alzheimer's disease (AD), also known as senile dementia, is a common neurodegenerative disease characterized by progressive cognitive impairment and personality changes. Numerous evidences have suggested that microRNAs (miRNAs) are involved in the pathogenesis and development of AD. However, the exact role of miR-335-5p in the progression of AD is still not clearly clarified. Methods: The protein and mRNA levels were measured by western blot and RNA extraction and quantitative real-time PCR (qRT-PCR), respectively. The relationship between miR-335-5p and c-jun-N-terminal kinase 3 (JNK3) was confirmed by dual-luciferase reporter assay. SH-SY5Y cells were transfected with APP mutant gene to establish the in vitro AD cell model. Flow cytometry and western blot were performed to evaluate cell apoptosis. The APP/PS1 transgenic mice were used as an in vivo AD model. Morris water maze test was performed to assess the effect of miR- 335-5p on the cognitive deficits in APP/PS1 transgenic mice. Results: The JNK3 mRNA expression and protein levels of JNK3 and β-Amyloid (Aβ) were significantly up-regulated, and the mRNA expression of miR-335-5p was down-regulated in the brain tissues of AD patients. The expression levels of miR-335-5p and JNK3 were significantly inversely correlated. Further, the dual Luciferase assay verified the relationship between miR-335- 5p and JNK3. Overexpression of miR-335-5p significantly decreased the protein levels of JNK3 and Aβ and inhibited apoptosis in SH-SY5Y/APPswe cells, whereas the inhibition of miR-335-5p obtained the opposite results. Moreover, the overexpression of miR-335-5p remarkably improved the cognitive abilities of APP/PS1 mice. Conclusion: The results revealed that the increased JNK3 expression, negatively regulated by miR-335-5p, may be a potential mechanism that contributes to Aβ accumulation and AD progression, indicating a novel approach for AD treatment.

A Biomarker Combining Imaging and Neuropsychological Assessment for Tracking Early Alzheimer's Disease in Clinical Trials

2018 ◽  
Vol 15 (5) ◽  
pp. 429-442 ◽  
Author(s):  
Nishant Verma ◽  
S. Natasha Beretvas ◽  
Belen Pascual ◽  
Joseph C. Masdeu ◽  
Mia K. Markey ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Trials ◽  
Cognitive Impairment ◽  
Latent Variable ◽  
Brain Regions ◽  
Disease Assessment ◽  
Latent Variable Analysis ◽  
The Relationship ◽  
Selection Of

Background: Combining optimized cognitive (Alzheimer's Disease Assessment Scale- Cognitive subscale, ADAS-Cog) and atrophy markers of Alzheimer's disease for tracking progression in clinical trials may provide greater sensitivity than currently used methods, which have yielded negative results in multiple recent trials. Furthermore, it is critical to clarify the relationship among the subcomponents yielded by cognitive and imaging testing, to address the symptomatic and anatomical variability of Alzheimer's disease. Method: Using latent variable analysis, we thoroughly investigated the relationship between cognitive impairment, as assessed on the ADAS-Cog, and cerebral atrophy. A biomarker was developed for Alzheimer's clinical trials that combines cognitive and atrophy markers. Results: Atrophy within specific brain regions was found to be closely related with impairment in cognitive domains of memory, language, and praxis. The proposed biomarker showed significantly better sensitivity in tracking progression of cognitive impairment than the ADAS-Cog in simulated trials and a real world problem. The biomarker also improved the selection of MCI patients (78.8±4.9% specificity at 80% sensitivity) that will evolve to Alzheimer's disease for clinical trials. Conclusion: The proposed biomarker provides a boost to the efficacy of clinical trials focused in the mild cognitive impairment (MCI) stage by significantly improving the sensitivity to detect treatment effects and improving the selection of MCI patients that will evolve to Alzheimer’s disease.

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